SOC Channels

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Xibao Liu - One of the best experts on this subject based on the ideXlab platform.

  • STIM-TRP Pathways
    Store-operated Ca2+ entry (SOCE) pathways, 2011
    Co-Authors: Indu S Ambudkar, Kwong Tai Cheng, Hwei Ling Ong, Xibao Liu
    Abstract:

    Store-operated Ca2+ entry (SOCE) is activated in response to depletion of the ER-Ca2+ stores. Upon Ca2+ store depletion, the ER Ca2+ sensor protein, STIM1, oligomerizes and moves to ER/PM junctional domains where it interacts with and activates Channels involved in SOCE; namely Orai and TRPC Channels. Orai1 is the primary pore-forming component of the highly Ca2+ selective CRAC channel. It is recruited to ER/PM junctional domains by STIM1 where it is gated via interaction with a specific C-terminal domain of STIM1. Thus Orai1 and STIM1 are sufficient for generation of functional CRAC Channels. Store depletion also leads to activation of relatively non-selective cation Channels, referred to SOC Channels that contribute to SOCE in several other cell types. TRPC1 contributes to endogenous SOCE and SOC channel function in many cells types. In these cells, TRPC1-mediated Ca2+ entry and cation currents are stimulated with either agonist or thapsigargin, and inhibited by low [Gd3+] and 10–20 μM 2APB (conditions that block SOCE). STIM1 also asSOCiates with and gates TRPC1 via electrostatic interaction between STIM1 (684KK685) and TRPC1 (639DD640). Further, functional Orai1 is required for activation of TRPC1-SOCE and this has been asSOCiated with recruitment of a TRPC1/STIM1/Orai1 complex. However, there is ongoing debate regarding the activation of TRPC1 by store depletion as well as the role of Orai1 and STIM1 in regulating its function. This chapter will summarize recent studies and concepts regarding the contributions of Orai1 and TRPC1 to SOCE. We will discuss major unresolved questions regarding functional interaction between Orai1 and TRPC1 as well as possible mechanisms involved in the regulation of TRPC Channels.

  • Local Ca2+ Entry Via Orai1 Regulates Plasma Membrane Recruitment of TRPC1 and Controls Cytosolic Ca2+ Signals Required for Specific Cell Functions
    PLoS biology, 2011
    Co-Authors: Kwong Tai Cheng, Xibao Liu, Hwei Ling Ong, William D Swaim, Indu S Ambudkar
    Abstract:

    Store-operated Ca2+ entry (SOCE) has been asSOCiated with two types of Channels: CRAC Channels that require Orai1 and STIM1 and SOC Channels that involve TRPC1, Orai1, and STIM1. While TRPC1 significantly contributes to SOCE and SOC channel activity, abrogation of Orai1 function eliminates SOCE and activation of TRPC1. The critical role of Orai1 in activation of TRPC1-SOC Channels following Ca2+ store depletion has not yet been established. Herein we report that TRPC1 and Orai1 are components of distinct Channels. We show that TRPC1/Orai1/STIM1-dependent ISOC, activated in response to Ca2+ store depletion, is composed of TRPC1/STIM1-mediated non-selective cation current and Orai1/STIM1-mediated ICRAC; the latter is detected when TRPC1 function is suppressed by expression of shTRPC1 or a STIM1 mutant that lacks TRPC1 gating, STIM1(684EE685). In addition to gating TRPC1 and Orai1, STIM1 mediates the recruitment and asSOCiation of the Channels within ER/PM junctional domains, a critical step in TRPC1 activation. Importantly, we show that Ca2+ entry via Orai1 triggers plasma membrane insertion of TRPC1, which is prevented by blocking SOCE with 1 µM Gd3+, removal of extracellular Ca2+, knockdown of Orai1, or expression of dominant negative mutant Orai1 lacking a functional pore, Orai1-E106Q. In cells expressing another pore mutant of Orai1, Orai1-E106D, TRPC1 trafficking is supported in Ca2+-containing, but not Ca2+-free, medium. Consistent with this, ICRAC is activated in cells pretreated with thapsigargin in Ca2+-free medium while ISOC is activated in cells pretreated in Ca2+-containing medium. Significantly, TRPC1 function is required for sustained KCa activity and contributes to NFκB activation while Orai1 is sufficient for NFAT activation. Together, these findings reveal an as-yet unidentified function for Orai1 that explains the critical requirement of the channel in the activation of TRPC1 following Ca2+ store depletion. We suggest that coordinated regulation of the surface expression of TRPC1 by Orai1 and gating by STIM1 provides a mechanism for rapidly modulating and maintaining SOCE-generated Ca2+ signals. By recruiting ion Channels and other signaling pathways, Orai1 and STIM1 concertedly impact a variety of critical cell functions that are initiated by SOCE.

  • Recent Progress in the Regulation of TRPC1 by Store Depletion
    2010
    Co-Authors: Indu S Ambudkar, Kwong Tai Cheng, Xibao Liu, Hwei Ling Ong, Timothy Lockwich
    Abstract:

    Store-operated Ca entry (SOCE) is activated in response to depletion of the ER-Ca stores. The ER-Ca 2+ sensor protein, STIM1, oligomerizes when [Ca ] in the store is decreased and moves to ER/PM junctional domains where it interacts with and activates Channels involved in SOCE, namely Orai and TRPC Channels. 2+ Orai1 is the primary pore-forming component of the highly Ca selective CRAC channel. It is recruited to ER/ PM junctional domains by STIM1 where it is gated via interaction with a specific C-terminal domain of STIM1. Thus Orai1 and STIM1 are sufficient for generation of functional CRAC Channels. Store depletion also leads to activation of relatively non-selective cation Channels, referred to as SOC Channels that contribute to SOCE in several other cell types. TRPC1 has been proposed as a possible candidate component of SOC Channels. 2+ TRPC1 contributes to endogenous SOCE in many cells types. In these cells, TRPC1-mediated Ca entry and 3+ cation currents are stimulated with either agonist or thapsigargin, and inhibited by low [Gd ] and 10-20 µM 2APB (conditions that block SOCE). STIM1 also asSOCiates with and gates TRPC1 via electrostatic interaction between STIM1 (684KK685) and TRPC1 (639DD640). Further, functional Orai1 is required for activation of TRPC1-SOCE and this has been asSOCiated with recruitment of a TRPC1/STIM1/Orai1 complex. However, there is ongoing debate regarding the activation of TRPC1 by store depletion as well as the role of Orai1 and STIM1 in regulating its function. This chapter will summarize recent studies and concepts regarding the contri- butions of Orai1 and TRPC1 to SOCE. We will discuss major unresolved questions regarding functional inter- action between Orai1 and TRPC1 as well as possible mechanisms involved in the regulation of TRPC Channels.

  • functional requirement for orai1 in store operated trpc1 stim1 Channels
    Journal of Biological Chemistry, 2008
    Co-Authors: Kwong Tai Cheng, Xibao Liu, Hwei Ling Ong, Indu S Ambudkar
    Abstract:

    Orai1 and TRPC1 have been proposed as core components of store-operated calcium release-activated calcium (CRAC) and store-operated calcium (SOC) Channels, respectively. STIM1, a Ca2+ sensor protein in the endoplasmic reticulum, interacts with and mediates store-dependent regulation of both Channels. We have previously reported that dynamic asSOCiation of Orai1, TRPC1, and STIM1 is involved in activation of store-operated Ca2+ entry (SOCE) in salivary gland cells. In this study, we have assessed the molecular basis of TRPC1-SOC Channels in HEK293 cells. We report that TRPC1+STIM1-dependent SOCE requires functional Orai1. Thapsigargin stimulation of cells expressing Orai1+STIM1 increased Ca2+ entry and activated typical ICRAC current. STIM1 alone did not affect SOCE, whereas expression of Orai1 induced a decrease. Expression of TRPC1 induced a small increase in SOCE, which was greatly enhanced by co-expression of STIM1. Thapsigargin stimulation of cells expressing TRPC1+STIM1 activated a non-selective cation current, ISOC, that was blocked by 1 μm Gd3+ and 2-APB. Knockdown of Orai1 decreased endogenous SOCE as well as SOCE with TRPC1 alone. siOrai1 also significantly reduced SOCE and ISOC in cells expressing TRPC1+STIM1. Expression of R91WOrai1 or E106QOrai1 induced similar attenuation of TRPC1+STIM1-dependent SOCE and ISOC, whereas expression of Orai1 with TRPC1+STIM1 resulted in SOCE that was larger than that with Orai1+STIM1 or TRPC1+STIM1 but not additive. Additionally, Orai1, E106QOrai1, and R91WOrai1 co-immunoprecipitated with similar levels of TRPC1 and STIM1 from HEK293 cells, and endogenous TRPC1, STIM1, and Orai1 were co-immunoprecipitated from salivary glands. Together, these data demonstrate a functional requirement for Orai1 in TRPC1+STIM1-dependent SOCE.

  • attenuation of store operated ca2 current impairs salivary gland fluid secretion in trpc1 mice
    Proceedings of the National Academy of Sciences of the United States of America, 2007
    Co-Authors: Xibao Liu, Kwong Tai Cheng, Bidhan C Bandyopadhyay, Biswaranjan Pani, Alexander Dietrich, Biman C Paria, William D Swaim, David J Beech, Eda Yildrim, Brij B Singh
    Abstract:

    Agonist-induced Ca2+ entry via store-operated Ca2+ (SOC) Channels is suggested to regulate a wide variety of cellular functions, including salivary gland fluid secretion. However, the molecular components of these Channels and their physiological function(s) are largely unknown. Here we report that attenuation of SOC current underlies salivary gland dysfunction in mice lacking transient receptor potential 1 (TRPC1). Neurotransmitter-regulated salivary gland fluid secretion in TRPC1-deficient TRPC1(−/−) mice was severely decreased (by 70%). Further, agonist- and thapsigargin-stimulated SOC channel activity was significantly reduced in salivary gland acinar cells isolated from TRPC1(−/−) mice. Deletion of TRPC1 also eliminated sustained Ca2+-dependent potassium channel activity, which depends on Ca2+ entry and is required for fluid secretion. Expression of key proteins involved in fluid secretion and Ca2+ signaling, including STIM1 and other TRPC Channels, was not altered. Together, these data demonstrate that reduced SOC entry accounts for the severe loss of salivary gland fluid secretion in TRPC1(−/−) mice. Thus, TRPC1 is a critical component of the SOC channel in salivary gland acinar cells and is essential for neurotransmitter-regulation of fluid secretion.

Kwong Tai Cheng - One of the best experts on this subject based on the ideXlab platform.

  • STIM-TRP Pathways
    Store-operated Ca2+ entry (SOCE) pathways, 2011
    Co-Authors: Indu S Ambudkar, Kwong Tai Cheng, Hwei Ling Ong, Xibao Liu
    Abstract:

    Store-operated Ca2+ entry (SOCE) is activated in response to depletion of the ER-Ca2+ stores. Upon Ca2+ store depletion, the ER Ca2+ sensor protein, STIM1, oligomerizes and moves to ER/PM junctional domains where it interacts with and activates Channels involved in SOCE; namely Orai and TRPC Channels. Orai1 is the primary pore-forming component of the highly Ca2+ selective CRAC channel. It is recruited to ER/PM junctional domains by STIM1 where it is gated via interaction with a specific C-terminal domain of STIM1. Thus Orai1 and STIM1 are sufficient for generation of functional CRAC Channels. Store depletion also leads to activation of relatively non-selective cation Channels, referred to SOC Channels that contribute to SOCE in several other cell types. TRPC1 contributes to endogenous SOCE and SOC channel function in many cells types. In these cells, TRPC1-mediated Ca2+ entry and cation currents are stimulated with either agonist or thapsigargin, and inhibited by low [Gd3+] and 10–20 μM 2APB (conditions that block SOCE). STIM1 also asSOCiates with and gates TRPC1 via electrostatic interaction between STIM1 (684KK685) and TRPC1 (639DD640). Further, functional Orai1 is required for activation of TRPC1-SOCE and this has been asSOCiated with recruitment of a TRPC1/STIM1/Orai1 complex. However, there is ongoing debate regarding the activation of TRPC1 by store depletion as well as the role of Orai1 and STIM1 in regulating its function. This chapter will summarize recent studies and concepts regarding the contributions of Orai1 and TRPC1 to SOCE. We will discuss major unresolved questions regarding functional interaction between Orai1 and TRPC1 as well as possible mechanisms involved in the regulation of TRPC Channels.

  • Local Ca2+ Entry Via Orai1 Regulates Plasma Membrane Recruitment of TRPC1 and Controls Cytosolic Ca2+ Signals Required for Specific Cell Functions
    PLoS biology, 2011
    Co-Authors: Kwong Tai Cheng, Xibao Liu, Hwei Ling Ong, William D Swaim, Indu S Ambudkar
    Abstract:

    Store-operated Ca2+ entry (SOCE) has been asSOCiated with two types of Channels: CRAC Channels that require Orai1 and STIM1 and SOC Channels that involve TRPC1, Orai1, and STIM1. While TRPC1 significantly contributes to SOCE and SOC channel activity, abrogation of Orai1 function eliminates SOCE and activation of TRPC1. The critical role of Orai1 in activation of TRPC1-SOC Channels following Ca2+ store depletion has not yet been established. Herein we report that TRPC1 and Orai1 are components of distinct Channels. We show that TRPC1/Orai1/STIM1-dependent ISOC, activated in response to Ca2+ store depletion, is composed of TRPC1/STIM1-mediated non-selective cation current and Orai1/STIM1-mediated ICRAC; the latter is detected when TRPC1 function is suppressed by expression of shTRPC1 or a STIM1 mutant that lacks TRPC1 gating, STIM1(684EE685). In addition to gating TRPC1 and Orai1, STIM1 mediates the recruitment and asSOCiation of the Channels within ER/PM junctional domains, a critical step in TRPC1 activation. Importantly, we show that Ca2+ entry via Orai1 triggers plasma membrane insertion of TRPC1, which is prevented by blocking SOCE with 1 µM Gd3+, removal of extracellular Ca2+, knockdown of Orai1, or expression of dominant negative mutant Orai1 lacking a functional pore, Orai1-E106Q. In cells expressing another pore mutant of Orai1, Orai1-E106D, TRPC1 trafficking is supported in Ca2+-containing, but not Ca2+-free, medium. Consistent with this, ICRAC is activated in cells pretreated with thapsigargin in Ca2+-free medium while ISOC is activated in cells pretreated in Ca2+-containing medium. Significantly, TRPC1 function is required for sustained KCa activity and contributes to NFκB activation while Orai1 is sufficient for NFAT activation. Together, these findings reveal an as-yet unidentified function for Orai1 that explains the critical requirement of the channel in the activation of TRPC1 following Ca2+ store depletion. We suggest that coordinated regulation of the surface expression of TRPC1 by Orai1 and gating by STIM1 provides a mechanism for rapidly modulating and maintaining SOCE-generated Ca2+ signals. By recruiting ion Channels and other signaling pathways, Orai1 and STIM1 concertedly impact a variety of critical cell functions that are initiated by SOCE.

  • Recent Progress in the Regulation of TRPC1 by Store Depletion
    2010
    Co-Authors: Indu S Ambudkar, Kwong Tai Cheng, Xibao Liu, Hwei Ling Ong, Timothy Lockwich
    Abstract:

    Store-operated Ca entry (SOCE) is activated in response to depletion of the ER-Ca stores. The ER-Ca 2+ sensor protein, STIM1, oligomerizes when [Ca ] in the store is decreased and moves to ER/PM junctional domains where it interacts with and activates Channels involved in SOCE, namely Orai and TRPC Channels. 2+ Orai1 is the primary pore-forming component of the highly Ca selective CRAC channel. It is recruited to ER/ PM junctional domains by STIM1 where it is gated via interaction with a specific C-terminal domain of STIM1. Thus Orai1 and STIM1 are sufficient for generation of functional CRAC Channels. Store depletion also leads to activation of relatively non-selective cation Channels, referred to as SOC Channels that contribute to SOCE in several other cell types. TRPC1 has been proposed as a possible candidate component of SOC Channels. 2+ TRPC1 contributes to endogenous SOCE in many cells types. In these cells, TRPC1-mediated Ca entry and 3+ cation currents are stimulated with either agonist or thapsigargin, and inhibited by low [Gd ] and 10-20 µM 2APB (conditions that block SOCE). STIM1 also asSOCiates with and gates TRPC1 via electrostatic interaction between STIM1 (684KK685) and TRPC1 (639DD640). Further, functional Orai1 is required for activation of TRPC1-SOCE and this has been asSOCiated with recruitment of a TRPC1/STIM1/Orai1 complex. However, there is ongoing debate regarding the activation of TRPC1 by store depletion as well as the role of Orai1 and STIM1 in regulating its function. This chapter will summarize recent studies and concepts regarding the contri- butions of Orai1 and TRPC1 to SOCE. We will discuss major unresolved questions regarding functional inter- action between Orai1 and TRPC1 as well as possible mechanisms involved in the regulation of TRPC Channels.

  • functional requirement for orai1 in store operated trpc1 stim1 Channels
    Journal of Biological Chemistry, 2008
    Co-Authors: Kwong Tai Cheng, Xibao Liu, Hwei Ling Ong, Indu S Ambudkar
    Abstract:

    Orai1 and TRPC1 have been proposed as core components of store-operated calcium release-activated calcium (CRAC) and store-operated calcium (SOC) Channels, respectively. STIM1, a Ca2+ sensor protein in the endoplasmic reticulum, interacts with and mediates store-dependent regulation of both Channels. We have previously reported that dynamic asSOCiation of Orai1, TRPC1, and STIM1 is involved in activation of store-operated Ca2+ entry (SOCE) in salivary gland cells. In this study, we have assessed the molecular basis of TRPC1-SOC Channels in HEK293 cells. We report that TRPC1+STIM1-dependent SOCE requires functional Orai1. Thapsigargin stimulation of cells expressing Orai1+STIM1 increased Ca2+ entry and activated typical ICRAC current. STIM1 alone did not affect SOCE, whereas expression of Orai1 induced a decrease. Expression of TRPC1 induced a small increase in SOCE, which was greatly enhanced by co-expression of STIM1. Thapsigargin stimulation of cells expressing TRPC1+STIM1 activated a non-selective cation current, ISOC, that was blocked by 1 μm Gd3+ and 2-APB. Knockdown of Orai1 decreased endogenous SOCE as well as SOCE with TRPC1 alone. siOrai1 also significantly reduced SOCE and ISOC in cells expressing TRPC1+STIM1. Expression of R91WOrai1 or E106QOrai1 induced similar attenuation of TRPC1+STIM1-dependent SOCE and ISOC, whereas expression of Orai1 with TRPC1+STIM1 resulted in SOCE that was larger than that with Orai1+STIM1 or TRPC1+STIM1 but not additive. Additionally, Orai1, E106QOrai1, and R91WOrai1 co-immunoprecipitated with similar levels of TRPC1 and STIM1 from HEK293 cells, and endogenous TRPC1, STIM1, and Orai1 were co-immunoprecipitated from salivary glands. Together, these data demonstrate a functional requirement for Orai1 in TRPC1+STIM1-dependent SOCE.

  • attenuation of store operated ca2 current impairs salivary gland fluid secretion in trpc1 mice
    Proceedings of the National Academy of Sciences of the United States of America, 2007
    Co-Authors: Xibao Liu, Kwong Tai Cheng, Bidhan C Bandyopadhyay, Biswaranjan Pani, Alexander Dietrich, Biman C Paria, William D Swaim, David J Beech, Eda Yildrim, Brij B Singh
    Abstract:

    Agonist-induced Ca2+ entry via store-operated Ca2+ (SOC) Channels is suggested to regulate a wide variety of cellular functions, including salivary gland fluid secretion. However, the molecular components of these Channels and their physiological function(s) are largely unknown. Here we report that attenuation of SOC current underlies salivary gland dysfunction in mice lacking transient receptor potential 1 (TRPC1). Neurotransmitter-regulated salivary gland fluid secretion in TRPC1-deficient TRPC1(−/−) mice was severely decreased (by 70%). Further, agonist- and thapsigargin-stimulated SOC channel activity was significantly reduced in salivary gland acinar cells isolated from TRPC1(−/−) mice. Deletion of TRPC1 also eliminated sustained Ca2+-dependent potassium channel activity, which depends on Ca2+ entry and is required for fluid secretion. Expression of key proteins involved in fluid secretion and Ca2+ signaling, including STIM1 and other TRPC Channels, was not altered. Together, these data demonstrate that reduced SOC entry accounts for the severe loss of salivary gland fluid secretion in TRPC1(−/−) mice. Thus, TRPC1 is a critical component of the SOC channel in salivary gland acinar cells and is essential for neurotransmitter-regulation of fluid secretion.

Brij B Singh - One of the best experts on this subject based on the ideXlab platform.

  • attenuation of store operated ca2 current impairs salivary gland fluid secretion in trpc1 mice
    Proceedings of the National Academy of Sciences of the United States of America, 2007
    Co-Authors: Xibao Liu, Kwong Tai Cheng, Bidhan C Bandyopadhyay, Biswaranjan Pani, Alexander Dietrich, Biman C Paria, William D Swaim, David J Beech, Eda Yildrim, Brij B Singh
    Abstract:

    Agonist-induced Ca2+ entry via store-operated Ca2+ (SOC) Channels is suggested to regulate a wide variety of cellular functions, including salivary gland fluid secretion. However, the molecular components of these Channels and their physiological function(s) are largely unknown. Here we report that attenuation of SOC current underlies salivary gland dysfunction in mice lacking transient receptor potential 1 (TRPC1). Neurotransmitter-regulated salivary gland fluid secretion in TRPC1-deficient TRPC1(−/−) mice was severely decreased (by 70%). Further, agonist- and thapsigargin-stimulated SOC channel activity was significantly reduced in salivary gland acinar cells isolated from TRPC1(−/−) mice. Deletion of TRPC1 also eliminated sustained Ca2+-dependent potassium channel activity, which depends on Ca2+ entry and is required for fluid secretion. Expression of key proteins involved in fluid secretion and Ca2+ signaling, including STIM1 and other TRPC Channels, was not altered. Together, these data demonstrate that reduced SOC entry accounts for the severe loss of salivary gland fluid secretion in TRPC1(−/−) mice. Thus, TRPC1 is a critical component of the SOC channel in salivary gland acinar cells and is essential for neurotransmitter-regulation of fluid secretion.

  • Attenuation of store-operated Ca2+ current impairs salivary gland fluid secretion in TRPC1(−/−) mice
    Proceedings of the National Academy of Sciences of the United States of America, 2007
    Co-Authors: Xibao Liu, Kwong Tai Cheng, Bidhan C Bandyopadhyay, Biswaranjan Pani, Alexander Dietrich, Biman C Paria, William D Swaim, David J Beech, Eda Yildrim, Brij B Singh
    Abstract:

    Agonist-induced Ca2+ entry via store-operated Ca2+ (SOC) Channels is suggested to regulate a wide variety of cellular functions, including salivary gland fluid secretion. However, the molecular components of these Channels and their physiological function(s) are largely unknown. Here we report that attenuation of SOC current underlies salivary gland dysfunction in mice lacking transient receptor potential 1 (TRPC1). Neurotransmitter-regulated salivary gland fluid secretion in TRPC1-deficient TRPC1(−/−) mice was severely decreased (by 70%). Further, agonist- and thapsigargin-stimulated SOC channel activity was significantly reduced in salivary gland acinar cells isolated from TRPC1(−/−) mice. Deletion of TRPC1 also eliminated sustained Ca2+-dependent potassium channel activity, which depends on Ca2+ entry and is required for fluid secretion. Expression of key proteins involved in fluid secretion and Ca2+ signaling, including STIM1 and other TRPC Channels, was not altered. Together, these data demonstrate that reduced SOC entry accounts for the severe loss of salivary gland fluid secretion in TRPC1(−/−) mice. Thus, TRPC1 is a critical component of the SOC channel in salivary gland acinar cells and is essential for neurotransmitter-regulation of fluid secretion.

  • dynamic assembly of trpc1 stim1 orai1 ternary complex is involved in store operated calcium influx evidence for similarities in store operated and calcium release activated calcium channel components
    Journal of Biological Chemistry, 2007
    Co-Authors: Hwei Ling Ong, Kwong Tai Cheng, Xibao Liu, Bidhan C Bandyopadhyay, Biswaranjan Pani, Biman C Paria, Jonathan Soboloff, Yousang Gwack, Sonal Srikanth, Brij B Singh
    Abstract:

    Store-operated calcium entry (SOCE) is a ubiquitous mechanism that is mediated by distinct SOC Channels, ranging from the highly selective calcium release-activated Ca2+ (CRAC) channel in rat basophilic leukemia and other hematopoietic cells to relatively Ca2+-selective or non-selective SOC Channels in other cells. Although the exact composition of these Channels is not yet established, TRPC1 contributes to SOC Channels and regulation of physiological function of a variety of cell types. Recently, Orai1 and STIM1 have been suggested to be sufficient for generating CRAC Channels. Here we show that Orai1 and STIM1 are also required for TRPC1-SOC Channels. Knockdown of TRPC1, Orai1, or STIM1 attenuated, whereas overexpression of TRPC1, but not Orai1 or STIM1, induced an increase in SOC entry and ISOC in human salivary gland cells. All three proteins were co-localized in the plasma membrane region of cells, and thapsigargin increased co-immunoprecipitation of TRPC1 with STIM1, and Orai1 in human salivary gland cells as well as dispersed mouse submandibular gland cells. In aggregate, the data presented here reveal that all three proteins are essential for generation of ISOC in these cells and that dynamic assembly of TRPC1-STIM1-Orai1 ternary complex is involved in activation of SOC channel in response to internal Ca2+ store depletion. Thus, these data suggest a common molecular basis for SOC and CRAC Channels.

Naim Akhtar Khan - One of the best experts on this subject based on the ideXlab platform.

  • zizyphin modulates calcium signalling in human taste bud cells and fat taste perception in the mouse
    Fundamental & Clinical Pharmacology, 2017
    Co-Authors: Babar Murtaza, Aziz Hichami, Meryem Berrichi, Chahid Bennamar, Thierry Tordjmann, Fatima Zohara Djeziri, Julia Leemput, Meriem Belarbi, Hakan Ozdener, Naim Akhtar Khan
    Abstract:

    Zizyphin, isolated from Zizyphus sps. leaf extracts, has been shown to modulate sugar taste perception, and the palatability of a sweet solution is increased by the addition of fatty acids. We, therefore, studied whether zizyphin also modulates fat taste perception. Zizyphin was purified from edible fruit of Zizyphus lotus L. Zizyphin induced increases in [Ca2+]i in human taste bud cells (hTBC). Zizyphin shared the endoplasmic reticulum Ca2+ pool and also recruited, in part, Ca2+ from extracellular environment via the opening of store-operated Ca2+ (SOC) Channels. Zizyphin exerted additive actions on linoleic acid-induced increases in [Ca2+]i in these cells, indicating that zizyphin does not exert its action via fatty acid receptors. However, zizyphin seemed to exert, at least in part, its action via bile acid receptor Takeda-G-protein-receptor-5 (TGR5) in hTBC. In behavioural tests, mice exhibited preference for both linoleic acid or zizyphin. Interestingly, zizyphin increased the preference for a solution containing-linoleic acid. The present study is the first evidence of the modulation of fat taste perception by zizyphin at the cellular level in hTBC. Our study might be helpful for considering the synthesis of zizyphin analogues as “taste modifiers” with a potential in the management of obesity and lipid-mediated disorders. This article is protected by copyright. All rights reserved.

  • cell mechanisms of gustatory lipids perception and modulation of the dietary fat preference
    Biochimie, 2014
    Co-Authors: Gado Dramane, Simon Akpona, Philippe Besnard, Naim Akhtar Khan
    Abstract:

    Abstract Dietary lipids are usually responsible of several metabolic disorders. Recent compelling evidences suggest that there is a sixth taste modality, destined for the detection of oro-gustatory fats. The lipid-binding glycoprotein CD36, expressed by circumvallate papillae (CVP) of the mouse tongue, has been shown to be implicated in oro-gustatory perception of dietary lipids. We demonstrate that linoleic acid (LA) by activating sPLA2, cPLA2 and iPLA2 via CD36, produced arachidonic acid (AA) and lyso-phosphatidylcholine (Lyso-PC) which triggered Ca2+ influx in CD36-positive taste bud cells (TBC), purified from mouse CVP. LA induced the production of Ca2+ influx factor (CIF). CIF, AA and Lyso-PC exerted different actions on the opening of store-operated Ca2+ (SOC) Channels, constituted of Orai proteins and regulated by STIM1, a sensor of Ca2+ depletion in the endoplasmic reticulum. We observed that CIF and Lyso-PC opened Orai1 Channels whereas AA-opened Ca2+ Channels were composed of Orai1/Orai3. STIM1 was found to regulate LA-induced CIF production and opening of both kinds of Ca2+ Channels. Furthermore, Stim1−/− mice lost the spontaneous preference for fat, observed in wild-type animals. Our results suggest that fatty acid-induced Ca2+ signaling, regulated by STIM1 via CD36, might be implicated in oro-gustatory perception of dietary lipids and the spontaneous preference for fat. Other cell types are involved in, and external factors can influence this preference.

  • oro gustatory perception of dietary lipids and calcium signaling in taste bud cells are altered in nutritionally obesity prone psammomys obesus
    PLOS ONE, 2013
    Co-Authors: Souleymane Abdoulazize, Hassimi Sadou, Feriel Atekmebarki, Arezki Bitam, E A Koceir, Naim Akhtar Khan
    Abstract:

    Since the increasing prevalence of obesity is one of the major health problems of the modern era, understanding the mechanisms of oro-gustatory detection of dietary fat is critical for the prevention and treatment of obesity. We have conducted the present study on Psammomys obesus, the rodent desert gerbil which is a unique polygenic natural animal model of obesity. Our results show that obese animals exhibit a strong preference for lipid solutions in a two-bottle test. Interestingly, the expression of CD36, a lipido-receptor, in taste buds cells (TBC), isolated from circumvallate papillae, was decreased at mRNA level, but remained unaltered at protein level, in obese animals. We further studied the effects of linoleic acid (LA), a long-chain fatty acid, on the increases in free intracellular calcium (Ca2+) concentrations, [Ca2+]i, in the TBC of P. obesus. LA induced increases in [Ca2+]i, largely via CD36, from intracellular pool, followed by the opening of store-operated Ca2+ (SOC) Channels in the TBC of these animals. The action of this fatty acid on the increases in [Ca2+]i was higher in obese animals than that in controls. However, the release of Ca2+ from intracellular stores, studied also by employing thapsigargin, was lower in TBC of obese animals than control rodents. In this study, we show, for the first time, that increased lipid intake and altered Ca2+ signaling in TBC are asSOCiated with obesity in Psammomys obesus.

  • Ca2+ signaling in taste bud cells and spontaneous preference for fat: Unresolved roles of CD36 and GPR120
    Biochimie, 2013
    Co-Authors: Souleymane Abdoul-azize, Hassimi Sadou, Subramaniam Selvakumar, Philippe Besnard, Naim Akhtar Khan
    Abstract:

    Abstract Recent compelling evidences from rodent and human studies raise the possibility for an additional sixth taste modality devoted to oro-gustatory perception of dietary lipids. Understanding the mechanisms underlying oro-gustatory detection of dietary fat is critical for the prevention and treatment of obesity. A number of studies have suggested that lingual CD36, a glycoprotein, highly expressed by circumvallate papillae of the tongue, is implicated in the perception of dietary fat taste. G protein-coupled receptors (GPCRs) are important signaling molecules for many aspects of cellular functions. It has been shown that these receptors, particularly GPR120, are also involved in lipid taste perception. We have shown that dietary long-chain fatty acids (LCFAs), in CD36-positive taste bud cells (TBC), induce increases in free intracellular Ca 2+ concentrations, [Ca 2+ ]i, by recruiting Ca 2+ from endoplasmic reticulum (ER) pool via inositol 1,4,5-triphosphate production, followed by Ca 2+ influx via opening of store-operated Ca 2+ (SOC) Channels. GPR120 is also coupled to increases in [Ca 2+ ]i by dietary fatty acids. We observed that stromal interaction molecule 1 (STIM1), a sensor of Ca 2+ depletion in the ER, mediated fatty acid-induced Ca 2+ signaling and spontaneous preference for fat in the mouse. In this review article, we discuss the recent advances and unresolved roles of CD36 and GPR120 in lipid taste signaling in taste bud cells.

  • STIM1 regulates calcium signaling in taste bud cells and preference for fat in mice.
    Journal of Clinical Investigation, 2012
    Co-Authors: Gado Dramane, Souleymane Abdoul-azize, Simon Akpona, Christophe Chouabe, Hassimi Sadou, Aziz Hichami, Bernhard Nieswandt, Timo Vogtle, Philippe Besnard, Naim Akhtar Khan
    Abstract:

    Understanding the mechanisms underlying oro-gustatory detection of dietary fat is critical for the prevention and treatment of obesity. The lipid-binding glycoprotein CD36, which is expressed by circumvallate papillae (CVP) of the mouse tongue, has been implicated in oro-gustatory perception of dietary lipids. Here, we demonstrate that stromal interaction molecule 1 (STIM1), a sensor of Ca2+ depletion in the endoplasmic reticulum, mediates fatty acid–induced Ca2+ signaling in the mouse tongue and fat preference. We showed that linoleic acid (LA) induced the production of arachidonic acid (AA) and lysophosphatidylcholine (Lyso-PC) by activating multiple phospholipase A2 isoforms via CD36. This activation triggered Ca2+ influx in CD36-positive taste bud cells (TBCs) purified from mouse CVP. LA also induced the production of Ca2+ influx factor (CIF). STIM1 was found to regulate LA-induced CIF production and the opening of multiple store-operated Ca2+ (SOC) Channels. Furthermore, CD36-positive TBCs from Stim1–/– mice failed to release serotonin, and Stim1–/– mice lost the spontaneous preference for fat that was observed in wild-type animals. Our results suggest that fatty acid–induced Ca2+ signaling, regulated by STIM1 via CD36, might be implicated in oro-gustatory perception of dietary lipids and the spontaneous preference for fat.

Juan A. Rosado - One of the best experts on this subject based on the ideXlab platform.

  • TRPC Channels in the SOCE Scenario.
    Cells, 2020
    Co-Authors: Jose J. Lopez, Tarik Smani, Isaac Jardin, Jose Sanchez-collado, Ginés M. Salido, Juan A. Rosado
    Abstract:

    Transient receptor potential (TRP) proteins form non-selective Ca2+ permeable Channels that contribute to the modulation of a number of physiological functions in a variety of cell types. Since the identification of TRP proteins in Drosophila, it is well known that these Channels are activated by stimuli that induce PIP2 hydrolysis. The canonical TRP (TRPC) Channels have long been suggested to be constituents of the store-operated Ca2+ (SOC) Channels; however, none of the TRPC Channels generate Ca2+ currents that resemble ICRAC. STIM1 and Orai1 have been identified as the components of the Ca2+ release-activated Ca2+ (CRAC) Channels and there is a body of evidence supporting that STIM1 is able to gate Orai1 and TRPC1 in order to mediate non-selective cation currents named ISOC. STIM1 has been found to interact to and activate Orai1 and TRPC1 by different mechanisms and the involvement of TRPC1 in store-operated Ca2+ entry requires both STIM1 and Orai1. In addition to the participation of TRPC1 in the ISOC currents, TRPC1 and other TRPC proteins might play a relevant role modulating Orai1 channel function. This review summarizes the functional role of TRPC Channels in the STIM1–Orai1 scenario.

  • Molecular Basis and Regulation of Store-Operated Calcium Entry.
    Advances in experimental medicine and biology, 2019
    Co-Authors: Jose J. Lopez, Tarik Smani, Isaac Jardin, Jose Sanchez-collado, Ginés M. Salido, Letizia Albarran, Carlos Cantonero, Juan A. Rosado
    Abstract:

    Store-operated Ca2+ entry (SOCE) is a ubiquitous mechanism for Ca2+ influx in mammalian cells with important physiological implications. Since the discovery of SOCE more than three decades ago, the mechanism that communicates the information about the amount of Ca2+ accumulated in the intracellular Ca2+ stores to the plasma membrane Channels and the nature of these Channels have been matters of intense investigation and debate. The stromal interaction molecule-1 (STIM1) has been identified as the Ca2+ sensor of the intracellular Ca2+ compartments that activates the store-operated Channels. STIM1 regulates two types of store-dependent Channels: the Ca2+ release-activated Ca2+ (CRAC) Channels, formed by Orai1 subunits, that conduct the highly Ca2+ selective current I CRAC and the cation permeable store-operated Ca2+ (SOC) Channels, which consist of Orai1 and TRPC1 proteins and conduct the non-selective current I SOC. While the crystal structure of Drosophila CRAC channel has already been solved, the architecture of the SOC Channels still remains unclear. The dynamic interaction of STIM1 with the store-operated Channels is modulated by a number of proteins that either support the formation of the functional STIM1-channel complex or protect the cell against Ca2+ overload.

  • STIM and calcium channel complexes in cancer.
    Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, 2016
    Co-Authors: Isaac Jardin, Juan A. Rosado
    Abstract:

    The ion Ca(2+) is a ubiquitous second messenger that mediates a variety of cellular functions. Dysfunction of the mechanisms involved in Ca(2+) homeostasis underlies a number of pathological processes, including cancer. Store-operated Ca(2+) entry (SOCE) is a major mechanism for Ca(2+) entry modulated by the intracellular Ca(2+) stores. The Ca(2+)-selective store-operated current (ICRAC) is mediated by the endoplasmic reticulum (ER) Ca(2+) sensor STIM1 and the store-operated Ca(2+) (SOC) channel Orai1, while other non-selective cation currents (ISOC) involves the participation of members of the canonical transient receptor potential (TRPC) channel family, including TRPC1. Distinct isoforms of the key components of SOCE have been described in mammalian cells, STIM1 and 2, Orai1-3 and TRPC1-7. In cancer cells, SOCE has been reported to play an important role in cell cycle progression and proliferation, migration, metastasis and evasion of apoptosis. Changes in the expression of the key elements of SOCE and Ca(2+) homeostasis remodeling have been account to play important roles in the phenotypic changes observed in transformed cells. Despite there are differences in the expression level of the molecular components of SOCE, as well as in the relevance of the STIM, Orai and TRPC isoforms in SOCE and tumorigenesis among cancer cell types, there is a body of evidence supporting an important role for SOCE underlying the phenotypic modifications of cancer cells that propose STIM and the SOC Channels as suitable candidate targets for future prognostic or therapeutic strategies. This article is part of a Special Issue entitled: Calcium and Cell Fate. Guest Editors: Jacques Haiech, Claus Heizmann, Joachim Krebs, Thierry Capiod and Olivier Mignen.

  • Homer proteins mediate the interaction between STIM1 and Cav1.2 Channels.
    Biochimica et biophysica acta, 2015
    Co-Authors: Natalia Dionisio, Tarik Smani, Ginés M. Salido, Geoffrey E. Woodard, Antonio Castellano, Juan A. Rosado
    Abstract:

    Abstract STIM1 is a ubiquitous Ca 2 + sensor of the intracellular, agonist-sensitive, Ca 2 + stores that communicates the filling state of the Ca 2 + compartments to plasma membrane store-operated Ca 2 + (SOC) Channels. STIM1 has been presented as a point of convergence between store-operated and voltage-operated Ca 2 + influx, both inducing activation of SOC Channels while suppressing Ca v 1.2 Channels. Here we report that Homer proteins play a relevant role in the communication between STIM1 and Ca v 1.2 Channels. HEK-293 cells transiently expressing Ca v 1.2 channel subunits α 1 , β 2 and α 2 δ–1 exhibited a significant Ca 2 + entry upon treatment with a high concentration of KCl. In Ca v 1.2-expressing cells, treatment with thapsigargin (TG), to induce passive discharge of the intracellular Ca 2 + stores, resulted in Ca 2 + influx that was significantly greater than in cells not expressing Ca v 1.2 Channels, a difference that was abolished by nifedipine and diltiazem. Treatment with TG induces co-immunoprecipitation of Homer1 with STIM1 and the Ca v 1.2 α 1 subunit. Impairment of Homer function by introduction of the synthetic PPKKFR peptide into cells, which emulates the proline-rich sequences of the PPXXF motif, or using siRNA Homer1, reduced the asSOCiation of STIM1 and the Ca v 1.2 α 1 subunit. These findings indicate that Homer is important for the asSOCiation between both proteins. Finally, treatment with siRNA Homer1 or the PPKKFR peptide enhanced the nifedipine-sensitive component of TG response in Ca v 1.2-expressing cells. Altogether, these findings provide evidence for a new role of Homer1 supporting the regulation of Cav1.2 Channels by STIM1.

  • Biochemical and functional properties of the store-operated Ca2+ Channels
    Cellular signalling, 2008
    Co-Authors: Ginés M. Salido, Stewart O. Sage, Juan A. Rosado
    Abstract:

    Abstract Store-operated calcium entry (SOCE) is a major mechanism for Ca2+ entry in excitable and non-excitable cells. The best-characterised store-operated current is ICRAC, but other currents activated by Ca2+ store depletion have also been reported. The recent identification of the proteins stromal interaction molecule 1 (STIM1) and Orai1 has shed new light on the nature and regulation of SOC Channels. STIM1 has been presented as the endoplasmic reticulum (ER) Ca2+ sensor that communicates the content of the Ca2+ stores to the store-operated Channels, a mechanism that involves redistribution of STIM1 to peripheral ER sites and co-clustering with the Ca2+ channel subunit, Orai1. Interestingly, TRPC1, which has long been proposed as a SOC channel candidate, asSOCiates with Orai1 and STIM1 in a ternary complex that appears to increase the variability of SOC currents available to modulate cell function.