The Experts below are selected from a list of 315 Experts worldwide ranked by ideXlab platform
Yoshiro Ishimaru - One of the best experts on this subject based on the ideXlab platform.
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the response of pkd1l3 PKD2L1 to acid stimuli is inhibited by capsaicin and its pungent analogs
FEBS Journal, 2012Co-Authors: Sho Ishii, Yoshiro Ishimaru, Azusa Kurokawa, Mikiya Kishi, Keigo Yamagami, Shinji Okada, Takumi MisakaAbstract:Polycystic kidney disease (PKD) 2L1 protein is a member of the transient receptor potential (TRP) ion channel family. In circumvallate and foliate papillae, PKD2L1 is coexpressed with PKD1L3. PKD2L1 and PKD1L3 interact through their transmembrane domain and the resulting heteromer PKD1L3/PKD2L1 owns a unique channel property called ‘off-responses’ to acid stimulation, although PKD2L1 does not own this property by itself. To define the pharmacological properties of the PKD1L3/PKD2L1 channel, we developed a new method to effectively evaluate channel activity using human embryonic kidney 293T cells in which the channel was heterologously expressed. This method was applied to screen substances that potentially regulate it. We found that capsaicin and its analogs, which are TRPV1 agonists, inhibited the response to acid stimuli and that the capsaicin inhibition was reversible with an IC50 of 32.5 μm. Capsaicin and its analogs are thus useful tools for physiological analysis of PKD1L3/PKD2L1 function. Database Nucleotide sequence data are available in the GenBank database under the accession numbers hTRPA1, BC148423 and hTRPV3, BC104866
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the single pore residue asp523 in PKD2L1 determines ca2 permeation of the pkd1l3 PKD2L1 complex
Biochemical and Biophysical Research Communications, 2011Co-Authors: Chisato Fujimoto, Yoshiro Ishimaru, Yuka Katano, Takumi Misaka, Tatsuya Yamasoba, Tomiko Asakura, Keiko AbeAbstract:Abstract The polycystic kidney disease 1-like 3 (PKD1L3)–polycystic kidney disease 2-like 1 (PKD2L1) complex functions as a Ca2+-permeable, non-selective cation channel that is activated by acid and its subsequent removal; this is called an off-response. In this study, we identified a single aspartic residue in PKD2L1 that is responsible for the Ca2+ permeation of the PKD1L3/PKD2L1 complex. Calcium imaging analysis using point mutants of negatively charged amino acids present in the putative pore regions of PKD1L3 and PKD2L1 revealed that neutralization of the aspartic residue in PKD2L1 (D523N), which is conserved among PKD2 family members, abolished Ca2+ permeation, despite robust cell surface expression. In contrast, neutralization of the other negatively charged residues of PKD1L3 (D2049N and E2072Q) and PKD2L1 (D525N and D530N) as well as substitution of Asp523 with a glutamate residue (D523E) had little effect on Ca2+ permeation properties. These results demonstrate that Asp523 in PKD2L1 is a key determinant of Ca2+ permeation into the PKD1L3/PKD2L1 complex and that PKD2L1 contributes to forming the pore of the PKD1L3/PKD2L1 channel.
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interaction between pkd1l3 and PKD2L1 through their transmembrane domains is required for localization of PKD2L1 at taste pores in taste cells of circumvallate and foliate papillae
The FASEB Journal, 2010Co-Authors: Yoshiro Ishimaru, Yuka Katano, Takumi Misaka, Tomiko Asakura, Hiroaki Matsunami, Kurumi Yamamoto, Masato Akiba, Richard Roberts, Keiko AbeAbstract:The polycystic kidney disease 1-like 3 (PKD1L3) and polycystic kidney disease 2-like 1 (PKD2L1) proteins have been proposed to form heteromers that function as sour taste receptors in mammals. Here, we show that PKD1L3 and PKD2L1 interact through their transmembrane domains, and not through the coiled-coil domain, by coimmunoprecipitation experiments using a series of deletion mutants. Deletion mutants lacking the critical interaction region were not transported to the cell surface and remained in the cytoplasm, whereas PKD1L3 and PKD2L1 proteins were expressed at the cell surface when both are transfected. Calcium imaging analysis revealed that neither the coiled-coil domain nor the EF-hand domain located in the C-terminal cytoplasmic tail of PKD2L1 was required for response on stimulation with an acidic solution. Finally, PKD2L1 did not localize to the taste pore but was distributed throughout the cytoplasm in taste cells of circumvallate and foliate papillae in PKD1L3−/− mice, whereas it localized to the taste pore in wild-type mice. Collectively, these results suggest that the interaction between PKD1L3 and PKD2L1 through their transmembrane domains is essential for proper trafficking of the channels to the cell surface in taste cells of circumvallate and foliate papillae and in cultured cells.—Ishimaru, Y., Katano, Y., Yamamoto, K., Akiba, M., Misaka, T., Roberts, R. W., Asakura, T., Matsunami, H., Abe, K. Interaction between PKD1L3 and PKD2L1 through their transmembrane domains is required for localization of PKD2L1 at taste pores in taste cells of circumvallate and foliate papillae.
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acetic acid activates pkd1l3 PKD2L1 channel a candidate sour taste receptor
Biochemical and Biophysical Research Communications, 2009Co-Authors: Sho Ishii, Yoshiro Ishimaru, Takumi Misaka, Mikiya Kishi, Takayuki Kaga, Keiko AbeAbstract:Abstract The polycystic kidney disease (PKD) 1L3–PKD2L1 channel is a candidate sour taste receptor expressed in mammalian taste receptor cells. Various acids are reported to activate PKD channels after the removal of the acid stimuli, but little information is available on the activation of these channels by acetic acid. It was difficult to analyze the PKD channel activation by acetic acid using Ca2+ imaging experiments because this acid induces a transient and nonspecific response in cultured cells. Here, we developed a novel method to evaluate PKD channel activation by acetic acid. Nonspecific responses were observed only over a short period after the application of acetic acid. In contrast, PKD channel activation evoked by acetic acid as well as citric acid was detected even at a later time point. This method revealed that PKD1L3–PKD2L1 channel activation by acetic acid was pH-dependent and occurred when the ambient pH was
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off response property of an acid activated cation channel complex pkd1l3 PKD2L1
EMBO Reports, 2008Co-Authors: Hitoshi Inada, Yoshiro Ishimaru, Hiroaki Matsunami, Fuminori Kawabata, Tohru Fushiki, Makoto TominagaAbstract:Ligand-gated ion channels are important in sensory and synaptic transduction. The PKD1L3–PKD2L1 channel complex is a sour taste receptor candidate that is activated by acids. Here, we report that the proton-activated PKD1L3–PKD2L1 ion channels have the unique ability to be activated after the removal of an acid stimulus. We refer to this property as the off-response (previously described as a delayed response). Electrophysiological analyses show that acid-induced responses are observed only after the removal of an acid solution at less than pH 3.0. A small increase in pH is sufficient for PKD1L3–PKD2L1 channel activation, after exposure to an acid at pH 2.5. These results indicate that this channel is a new type of ion channel—designated as an ‘off-channel'—which is activated during stimulus application but not gated open until the removal of the stimulus. The off-response property of PKD1L3–PKD2L1 channels might explain the physiological phenomena occurring during sour taste sensation.
Sue C. Kinnamon - One of the best experts on this subject based on the ideXlab platform.
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physiological and behavioral responses to optogenetic stimulation of PKD2L1 type iii taste cells
eNeuro, 2019Co-Authors: Courtney E. Wilson, Aurelie Vandenbeuch, Sue C. KinnamonAbstract:Type III taste cells in mammalian taste buds are implicated in the detection and communication of sour and some salty stimuli, as well as carbonation and water. With this variety of proposed roles, it is unclear what information activated type III cells are communicating to the CNS. To better elucidate the role of type III cells in the taste bud, we use a type III cell-specific protein (polycystic kidney disease 2-like 1) to drive Cre-dependent expression of light-sensitive channelrhodopsin (Ai32) in mouse type III taste cells. Activation of these cells with light produces a taste nerve response in both the chorda tympani and glossopharyngeal nerves, and elicits a slight but significant aversion in two-bottle preference tests in both male and female mice. Unlike previous reports (Zocchi et al., 2017), our mice did not react to blue light stimulation with sustained drinking responses. These data suggest that type III cells are capable of communicating the presence of aversive stimuli in the oral cavity, which is in line with their responsiveness to sour and high concentrations of salt stimuli.
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Type III Cells in Anterior Taste Fields Are More Immunohistochemically Diverse Than Those of Posterior Taste Fields in Mice.
Chemical senses, 2017Co-Authors: Courtney E. Wilson, Thomas E. Finger, Sue C. KinnamonAbstract:Activation of Type III cells in mammalian taste buds is implicated in the transduction of acids (sour) and salty stimuli. Several lines of evidence suggest that function of Type III cells in the anterior taste fields may differ from that of Type III cells in posterior taste fields. Underlying anatomy to support this observation is, however, scant. Most existing immunohistochemical data characterizing this cell type focus on circumvallate taste buds in the posterior tongue. Equivalent data from anterior taste fields-fungiform papillae and soft palate-are lacking. Here, we compare Type III cells in four taste fields: fungiform, soft palate, circumvallate, and foliate in terms of reactivity to four canonical markers of Type III cells: polycystic kidney disease 2-like 1 (PKD2L1), synaptosomal associated protein 25 (SNAP25), serotonin (5-HT), and glutamate decarboxylase 67 (GAD67). Our findings indicate that while PKD2L1, 5-HT, and SNAP25 are highly coincident in posterior taste fields, they diverge in anterior taste fields. In particular, a subset of taste cells expresses PKD2L1 without the synaptic markers, and a subset of SNAP25 cells lacks expression of PKD2L1. In posterior taste fields, GAD67-positive cells are a subset of PKD2L1 expressing taste cells, but anterior taste fields also contain a significant population of GAD67-only expressing cells. These differences in expression patterns may underlie the observed functional differences between anterior and posterior taste fields.
Bryan D Moyer - One of the best experts on this subject based on the ideXlab platform.
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Genes encoding transmembrane proteins are expressed in human CV taste buds.
2013Co-Authors: Bryan D Moyer, Fernando Echeverri, Bianca Laita, Dalia Kalabat, Peter Hevezi, Na Gao, Hortensia Soto, Shaoyang Anthony Yeh, Mark ZollerAbstract:Section of human CV papilla before (A) and after (B) laser capture microdissection of taste buds. Collected taste bud regions (C), were isolated from CV papilla and used for molecular analysis of gene expression. A laser beam was used to cut the perimeter of taste buds and physically separate them from surrounding lingual epithelium. Taste buds were next lifted away from the tissue section with an adhesive cap. Panel C is an image of six isolated taste bud regions, devoid of surrounding lingual epithelium and connective tissue, on the adhesive cap. Scale bar is 40µm. Semi-quantitative PCR (D) for known taste genes (TRPM5 and PKD2L1), genes predicted or known to encode transmembrane proteins, and the housekeeping gene GAPDH in isolated CV taste buds (black bars) or non-gustatory lingual epithelium (white bars) collected by laser capture microdissection. Relative expression is shown on a logarithmic scale.
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Voltage-gated sodium channels in taste bud cells
BMC Neuroscience, 2009Co-Authors: Min Lu, Fernando Echeverri, Bianca Laita, Dalia Kalabat, Mark E Williams, Peter Hevezi, Albert Zlotnik, Bryan D MoyerAbstract:Background Taste bud cells transmit information regarding the contents of food from taste receptors embedded in apical microvilli to gustatory nerve fibers innervating basolateral membranes. In particular, taste cells depolarize, activate voltage-gated sodium channels, and fire action potentials in response to tastants. Initial cell depolarization is attributable to sodium influx through TRPM5 in sweet, bitter, and umami cells and an undetermined cation influx through an ion channel in sour cells expressing PKD2L1, a candidate sour taste receptor. The molecular identity of the voltage-gated sodium channels that sense depolarizing signals and subsequently initiate action potentials coding taste information to gustatory nerve fibers is unknown. Results We describe the molecular and histological expression profiles of cation channels involved in electrical signal transmission from apical to basolateral membrane domains. TRPM5 was positioned immediately beneath tight junctions to receive calcium signals originating from sweet, bitter, and umami receptor activation, while PKD2L1 was positioned at the taste pore. Using mouse taste bud and lingual epithelial cells collected by laser capture microdissection, SCN2A, SCN3A, and SCN9A voltage-gated sodium channel transcripts were expressed in taste tissue. SCN2A, SCN3A, and SCN9A were expressed beneath tight junctions in subsets of taste cells. SCN3A and SCN9A were expressed in TRPM5 cells, while SCN2A was expressed in TRPM5 and PKD2L1 cells. HCN4, a gene previously implicated in sour taste, was expressed in PKD2L1 cells and localized to cell processes beneath the taste pore. Conclusion SCN2A, SCN3A and SCN9A voltage-gated sodium channels are positioned to sense initial depolarizing signals stemming from taste receptor activation and initiate taste cell action potentials. SCN2A, SCN3A and SCN9A gene products likely account for the tetrodotoxin-sensitive sodium currents in taste receptor cells.
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voltage gated sodium channels in taste bud cells
BMC Neuroscience, 2009Co-Authors: Na Gao, Fernando Echeverri, Bianca Laita, Dalia Kalabat, Peter Hevezi, Albert Zlotnik, Mark Williams, Bryan D MoyerAbstract:Background Taste bud cells transmit information regarding the contents of food from taste receptors embedded in apical microvilli to gustatory nerve fibers innervating basolateral membranes. In particular, taste cells depolarize, activate voltage-gated sodium channels, and fire action potentials in response to tastants. Initial cell depolarization is attributable to sodium influx through TRPM5 in sweet, bitter, and umami cells and an undetermined cation influx through an ion channel in sour cells expressing PKD2L1, a candidate sour taste receptor. The molecular identity of the voltage-gated sodium channels that sense depolarizing signals and subsequently initiate action potentials coding taste information to gustatory nerve fibers is unknown.
Thomas E. Finger - One of the best experts on this subject based on the ideXlab platform.
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Type III Cells in Anterior Taste Fields Are More Immunohistochemically Diverse Than Those of Posterior Taste Fields in Mice.
Chemical senses, 2017Co-Authors: Courtney E. Wilson, Thomas E. Finger, Sue C. KinnamonAbstract:Activation of Type III cells in mammalian taste buds is implicated in the transduction of acids (sour) and salty stimuli. Several lines of evidence suggest that function of Type III cells in the anterior taste fields may differ from that of Type III cells in posterior taste fields. Underlying anatomy to support this observation is, however, scant. Most existing immunohistochemical data characterizing this cell type focus on circumvallate taste buds in the posterior tongue. Equivalent data from anterior taste fields-fungiform papillae and soft palate-are lacking. Here, we compare Type III cells in four taste fields: fungiform, soft palate, circumvallate, and foliate in terms of reactivity to four canonical markers of Type III cells: polycystic kidney disease 2-like 1 (PKD2L1), synaptosomal associated protein 25 (SNAP25), serotonin (5-HT), and glutamate decarboxylase 67 (GAD67). Our findings indicate that while PKD2L1, 5-HT, and SNAP25 are highly coincident in posterior taste fields, they diverge in anterior taste fields. In particular, a subset of taste cells expresses PKD2L1 without the synaptic markers, and a subset of SNAP25 cells lacks expression of PKD2L1. In posterior taste fields, GAD67-positive cells are a subset of PKD2L1 expressing taste cells, but anterior taste fields also contain a significant population of GAD67-only expressing cells. These differences in expression patterns may underlie the observed functional differences between anterior and posterior taste fields.
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the candidate sour taste receptor PKD2L1 is expressed by type iii taste cells in the mouse
Chemical Senses, 2008Co-Authors: Shinji Kataoka, Yoshiro Ishimaru, Ruibiao Yang, Hiroaki Matsunami, Jean Sevigny, John C Kinnamon, Thomas E. FingerAbstract:The transient receptor potential (TRP) channel, PKD2L1, is reported to be a candidate receptor for sour taste based on molecular biological and functional studies. Here, we investigated the expression pattern of PKD2L1-immunoreactivity (IR) in taste buds of the mouse. PKD2L1-IR is present in a few elongate cells in each taste bud as reported previously. The PKD2L1-expressing cells are different from those expressing PLCβ2, a marker of Type II cells. Likewise PKD2L1-immunoreactive taste cells do not express ecto-ATPase which marks Type I cells. The PKD2L1 positive cells are immunoreactive for NCAM, serotonin, PGP-9.5 (ubiquitin carboxy terminal transferase) and chromogranin A, all of which are present in Type III taste cells. At the ultrastructural level, PKD2L1-immunoreactive cells form synapses onto afferent nerve fibers, another feature of Type III taste cells. These results are consistent with the idea that different taste cells in each taste bud perform distinct functions. We suggest that Type III cells are necessary for transduction and/or transmission of information about “sour”, but have little or no role in transmission of taste information of other taste qualities.
Hiroaki Matsunami - One of the best experts on this subject based on the ideXlab platform.
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interaction between pkd1l3 and PKD2L1 through their transmembrane domains is required for localization of PKD2L1 at taste pores in taste cells of circumvallate and foliate papillae
The FASEB Journal, 2010Co-Authors: Yoshiro Ishimaru, Yuka Katano, Takumi Misaka, Tomiko Asakura, Hiroaki Matsunami, Kurumi Yamamoto, Masato Akiba, Richard Roberts, Keiko AbeAbstract:The polycystic kidney disease 1-like 3 (PKD1L3) and polycystic kidney disease 2-like 1 (PKD2L1) proteins have been proposed to form heteromers that function as sour taste receptors in mammals. Here, we show that PKD1L3 and PKD2L1 interact through their transmembrane domains, and not through the coiled-coil domain, by coimmunoprecipitation experiments using a series of deletion mutants. Deletion mutants lacking the critical interaction region were not transported to the cell surface and remained in the cytoplasm, whereas PKD1L3 and PKD2L1 proteins were expressed at the cell surface when both are transfected. Calcium imaging analysis revealed that neither the coiled-coil domain nor the EF-hand domain located in the C-terminal cytoplasmic tail of PKD2L1 was required for response on stimulation with an acidic solution. Finally, PKD2L1 did not localize to the taste pore but was distributed throughout the cytoplasm in taste cells of circumvallate and foliate papillae in PKD1L3−/− mice, whereas it localized to the taste pore in wild-type mice. Collectively, these results suggest that the interaction between PKD1L3 and PKD2L1 through their transmembrane domains is essential for proper trafficking of the channels to the cell surface in taste cells of circumvallate and foliate papillae and in cultured cells.—Ishimaru, Y., Katano, Y., Yamamoto, K., Akiba, M., Misaka, T., Roberts, R. W., Asakura, T., Matsunami, H., Abe, K. Interaction between PKD1L3 and PKD2L1 through their transmembrane domains is required for localization of PKD2L1 at taste pores in taste cells of circumvallate and foliate papillae.
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off response property of an acid activated cation channel complex pkd1l3 PKD2L1
EMBO Reports, 2008Co-Authors: Hitoshi Inada, Yoshiro Ishimaru, Hiroaki Matsunami, Fuminori Kawabata, Tohru Fushiki, Makoto TominagaAbstract:Ligand-gated ion channels are important in sensory and synaptic transduction. The PKD1L3–PKD2L1 channel complex is a sour taste receptor candidate that is activated by acids. Here, we report that the proton-activated PKD1L3–PKD2L1 ion channels have the unique ability to be activated after the removal of an acid stimulus. We refer to this property as the off-response (previously described as a delayed response). Electrophysiological analyses show that acid-induced responses are observed only after the removal of an acid solution at less than pH 3.0. A small increase in pH is sufficient for PKD1L3–PKD2L1 channel activation, after exposure to an acid at pH 2.5. These results indicate that this channel is a new type of ion channel—designated as an ‘off-channel'—which is activated during stimulus application but not gated open until the removal of the stimulus. The off-response property of PKD1L3–PKD2L1 channels might explain the physiological phenomena occurring during sour taste sensation.
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the candidate sour taste receptor PKD2L1 is expressed by type iii taste cells in the mouse
Chemical Senses, 2008Co-Authors: Shinji Kataoka, Yoshiro Ishimaru, Ruibiao Yang, Hiroaki Matsunami, Jean Sevigny, John C Kinnamon, Thomas E. FingerAbstract:The transient receptor potential (TRP) channel, PKD2L1, is reported to be a candidate receptor for sour taste based on molecular biological and functional studies. Here, we investigated the expression pattern of PKD2L1-immunoreactivity (IR) in taste buds of the mouse. PKD2L1-IR is present in a few elongate cells in each taste bud as reported previously. The PKD2L1-expressing cells are different from those expressing PLCβ2, a marker of Type II cells. Likewise PKD2L1-immunoreactive taste cells do not express ecto-ATPase which marks Type I cells. The PKD2L1 positive cells are immunoreactive for NCAM, serotonin, PGP-9.5 (ubiquitin carboxy terminal transferase) and chromogranin A, all of which are present in Type III taste cells. At the ultrastructural level, PKD2L1-immunoreactive cells form synapses onto afferent nerve fibers, another feature of Type III taste cells. These results are consistent with the idea that different taste cells in each taste bud perform distinct functions. We suggest that Type III cells are necessary for transduction and/or transmission of information about “sour”, but have little or no role in transmission of taste information of other taste qualities.
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transient receptor potential family members pkd1l3 and PKD2L1 form a candidate sour taste receptor
Proceedings of the National Academy of Sciences of the United States of America, 2006Co-Authors: Yoshiro Ishimaru, Makoto Tominaga, Hitoshi Inada, Momoka Kubota, Hanyi Zhuang, Hiroaki MatsunamiAbstract:Animals use their gustatory systems to evaluate the nutritious value, toxicity, sodium content, and acidity of food. Although characterization of molecular identities that receive taste chemicals is essential, molecular receptors underlying sour taste sensation remain unclear. Here, we show that two transient receptor potential (TRP) channel members, PKD1L3 and PKD2L1, are coexpressed in a subset of taste receptor cells in specific taste areas. Cells expressing these molecules are distinct from taste cells having receptors for bitter, sweet, or umami tastants. The PKD2L1 proteins are accumulated at the taste pore region, where taste chemicals are detected. PKD1L3 and PKD2L1 proteins can interact with each other, and coexpression of the PKD1L3 and PKD2L1 is necessary for their functional cell surface expression. Finally, PKD1L3 and PKD2L1 are activated by various acids when coexpressed in heterologous cells but not by other classes of tastants. These results suggest that PKD1L3 and PKD2L1 heteromers may function as sour taste receptors.