The Experts below are selected from a list of 678 Experts worldwide ranked by ideXlab platform
Kartik Venkatachalam - One of the best experts on this subject based on the ideXlab platform.
-
The role of TRPMLs in endolysosomal trafficking and function.
Cell Calcium, 2014Co-Authors: Kartik Venkatachalam, Chingon WongAbstract:Abstract Members of the Transient Receptor Potential-Mucolipin (TRPML) constitute a family of evolutionarily conserved cation channels that function predominantly in endolysosomal vesicles. Whereas loss-of-function mutations in human TRPML1 were first identified as being causative for the lysosomal storage disease, Mucolipidosis type IV, most mammals also express two other TRPML isoforms called TRPML2 and TRPML3. All three mammalian TRPMLs as well as TRPML related genes in other species including Caenorhabditis elegans and Drosophila exhibit overlapping functional and biophysical properties. The functions of TRPML proteins include roles in vesicular trafficking and biogenesis, maintenance of neuronal development, function, and viability, and regulation of intracellular and organellar ionic homeostasis. Biophysically, TRPML channels are non-selective cation channels exhibiting variable permeability to a host of cations including Na + , Ca 2+ , Fe 2+ , and Zn 2+ , and are activated by a phosphoinositide species, PI(3,5)P 2 , that is mostly found in endolysosomal membranes. Here, we review the functional and biophysical properties of these enigmatic cation channels, which represent the most ancient and archetypical TRP channels.
-
drosophila TRPML forms pi 3 5 p2 activated cation channels in both endolysosomes and plasma membrane
Journal of Biological Chemistry, 2014Co-Authors: Xinghua Feng, Yu Huang, Yungang Lu, Jian Xiong, Chingon Wong, Pu Yang, De Chen, Guangwei Du, Kartik VenkatachalamAbstract:Transient Receptor Potential mucolipin (TRPML) channels are implicated in endolysosomal trafficking, lysosomal Ca2+ and Fe2+ release, lysosomal biogenesis, and autophagy. Mutations in human TRPML1 cause the lysosome storage disease, mucolipidosis type IV (MLIV). Unlike vertebrates, which express three TRPML genes, TRPML1–3, the Drosophila genome encodes a single TRPML gene. Although the TRPML-deficient flies exhibit cellular defects similar to those in mammalian TRPML1 mutants, the biophysical properties of Drosophila TRPML channel remained uncharacterized. Here, we show that transgenic expression of human TRPML1 in the neurons of Drosophila TRPML mutants partially suppressed the pupal lethality phenotype. When expressed in HEK293 cells, Drosophila TRPML was localized in both endolysosomes and plasma membrane and was activated by phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2) applied to the cytoplasmic side in whole lysosomes and inside-out patches excised from plasma membrane. The PI(3,5)P2-evoked currents were blocked by phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), but not other phosphoinositides. Using TRPML A487P, which mimics the varitint-waddler (Va) mutant of mouse TRPML3 with constitutive whole-cell currents, we show that TRPML is biphasically regulated by extracytosolic pH, with an optimal pH about 0.6 pH unit higher than that of human TRPML1. In addition to monovalent cations, TRPML exhibits high permeability to Ca2+, Mn2+, and Fe2+, but not Fe3+. The TRPML currents were inhibited by trivalent cations Fe3+, La3+, and Gd3+. These features resemble more closely to mammalian TRPML1 than TRPML2 and TRPML3, but with some obvious differences. Together, our data support the use of Drosophila for assessing functional significance of TRPML1 in cell physiology.
-
feast or famine role of TRPML in preventing cellular amino acid starvation
Autophagy, 2013Co-Authors: Kartik Venkatachalam, Chingon Wong, Craig MontellAbstract:Lysosomal storage diseases are metabolic disorders characterized by the accumulation of acidic vacuoles, and are usually the consequence of the deficiency of an enzyme responsible for the metabolism of vesicular lipids, proteins or carbohydrates. In contrast, mucolipidosis type IV (MLIV), results from the absence of a vesicular Ca2+ release channel called mucolipin 1/transient receptor potential mucolipin 1 (MCOLN1/TRPML1) which is required for the fusion of amphisomes with lysosomes. In Drosophila, ablation of the MCOLN1 homolog (TRPML) leads to diminished viability during pupation when the animals rely on autophagy for nutrients. This pupal lethality results from decreased target of rapamycin complex 1 (TORC1) signaling, and is reversed by reactivating TORC1. Our findings indicate that one of the primary causes of toxicity in the absence of TRPML is cellular amino acid starvation, and the resulting decrease in TORC1 activity. Furthermore, our findings raise the intriguing possibility that the neurologic...
-
drosophila TRPML is required for torc1 activation
Current Biology, 2012Co-Authors: Chingon Wong, Craig Montell, Ruoxia Li, Kartik VenkatachalamAbstract:Summary Loss-of-function mutations in TRPML1 (transient receptor potential mucolipin 1) cause the lysosomal storage disorder, mucolipidosis type IV (MLIV). Here, we report that flies lacking the TRPML1 homolog displayed incomplete autophagy and reduced viability during the pupal period—a phase when animals rely on autophagy for nutrients. We show that TRPML was required for fusion of amphisomes with lysosomes, and its absence led to accumulation of vesicles of significantly larger volume and higher luminal Ca 2+ . We also found that TRPML 1 mutant cells showed decreased TORC1 (target of rapamycin complex 1) signaling and a concomitant upregulation of autophagy induction. Both of these defects in the mutants were reversed by genetically activating TORC1 or by feeding the larvae a high-protein diet. The high-protein diet also reduced the pupal lethality and the increased volume of acidic vesicles. Conversely, further inhibition of TORC1 activity by rapamycin exacerbated the mutant phenotypes. Finally, TORC1 exerted reciprocal control on TRPML function. A high-protein diet caused cortical localization of TRPML, and this effect was blocked by rapamycin. Our findings delineate the interrelationship between the TRPML and TORC1 pathways and raise the intriguing possibility that a high-protein diet might reduce the severity of MLIV.
-
Motor Deficit in a Drosophila Model of Mucolipidosis Type IV due to Defective Clearance of Apoptotic Cells
Cell, 2008Co-Authors: Kartik Venkatachalam, A. Ashleigh Long, Rebecca Elsaesser, Daria Nikolaeva, Kendal Broadie, Craig MontellAbstract:Summary Disruption of the Transient Receptor Potential (TRP) mucolipin 1 (TRPML1) channel results in the neurodegenerative disorder mucolipidosis type IV (MLIV), a lysosomal storage disease with severe motor impairments. The mechanisms underlying MLIV are poorly understood and there is no treatment. Here, we report a Drosophila MLIV model, which recapitulates the key disease features, including abnormal intracellular accumulation of macromolecules, motor defects, and neurodegeneration. The basis for the buildup of macromolecules was defective autophagy, which resulted in oxidative stress and impaired synaptic transmission. Late-apoptotic cells accumulated in TRPML mutant brains, suggesting diminished cell clearance. The accumulation of late-apoptotic cells and motor deficits were suppressed by expression of TRPML + in neurons, glia, or hematopoietic cells. We conclude that the neurodegeneration and motor defects result primarily from decreased clearance of apoptotic cells. Since hematopoietic cells in humans are involved in clearance of apoptotic cells, our results raise the possibility that bone marrow transplantation may limit the progression of MLIV.
Christian Grimm - One of the best experts on this subject based on the ideXlab platform.
-
TRPML cation channels in inflammation and immunity
Frontiers in Immunology, 2020Co-Authors: Barbara Spix, Yukai Chao, Carla Abrahamian, Chengchang Chen, Christian GrimmAbstract:Background: In 1883, Ilya Mechnikov discovered phagocytes and established the concept of phagocytosis by macrophages. In 1908, he was awarded the Nobel Prize in Physiology/Medicine for his findings, which laid the foundations for today's understanding of the innate immune response. Only in the 1960s, Max Cooper and Robert Good significantly advanced our understanding of the immune system by demonstrating that B- and T-cells cooperate to regulate the adaptive immune response. Both, innate and adaptive immune response are essential to effectively protect the individual against infectious agents, such as viruses, bacterial or insect toxins, or allergens. Innate immune responses occur rapidly upon exposure to noxious or infectious agents or organisms, in contrast to the adaptive immune system that needs days rather than hours to develop and acts primarily on the basis of antigen-specific receptors expressed on the surface of B- and T-lymphocytes. In recent years, it has become evident that endosomes and lysosomes are involved in many aspects of immune cell function, such as phagocytosis, antigen presentation and processing by antigen-presenting cells, release of proinflammatory mediators, e.g., by mast cells, or secretion of the pore-forming protein perforin by cytotoxic T lymphocytes. Several lysosomal storage disorders (LSDs) have been associated with defects in immune system function or immune system hyperactivity, such as Gaucher, Fabry, or Niemann-Pick type C1 disease, mucopolysaccharidoses (MPS), gangliosidosis, or juvenile neuronal ceroid lipofuscinosis (JNCL). Beside accumulating evidence on the importance of endolysosomes in immune cell function, recent results suggest direct roles of endolysosomal ion channels, such as the TRPML channels (mucolipins), which are members of the transient receptor potential (TRP) superfamily of non-selective cation channels, for different aspects of immune cell function. The aim of this review is to discuss the current knowledge about the roles of TRPML channels in inflammation and immunity, and to assess their potential as drug targets to influence immune cell functions. Advances: Examples of recently established roles of TRPML channels in immune system function and immune response include the TRPML1-mediated modulation of secretory lysosomes, granzyme B content, and tuning of effector function in NK cells, TRPML1-dependent directional dendritic cell (DC) migration and DC chemotaxis, and the role of TRPML2 in chemokine release from LPS-stimulated macrophages. Outlook: Although our understanding of the functional roles of TRPML channels in inflammation and immunity is still in its infancy, a few interesting findings have been made in the past years, encouraging further and more detailed work on the role of TRPMLs, e.g., in intracellular trafficking and release of chemokines, cytokines, or granzyme B, or in phagocytosis and bacterial toxin and virus trafficking through the endolysosomal machinery.
-
The protein interaction networks of mucolipins and two-pore channels
Biochimica et Biophysica Acta, 2018Co-Authors: Einar K Krogsaeter, Martin Biel, Christian Wahl-schott, Christian GrimmAbstract:Abstract Background The endolysosomal, non-selective cation channels, two-pore channels (TPCs) and mucolipins (TRPMLs), regulate intracellular membrane dynamics and autophagy. While partially compensatory for each other, isoform-specific intracellular distribution, cell-type expression patterns, and regulatory mechanisms suggest different channel isoforms confer distinct properties to the cell. Scope of review Briefly, established TPC/TRPML functions and interaction partners (‘interactomes’) are discussed. Novel TRPML3 interactors are shown, and a meta-analysis of experimentally obtained channel interactomes conducted. Accordingly, interactomes are compared and contrasted, and subsequently described in detail for TPC1, TPC2, TRPML1, and TRPML3. Major conclusions TPC interactomes are well-defined, encompassing intracellular membrane organisation proteins. TRPML interactomes are varied, encompassing cardiac contractility- and chaperone-mediated autophagy proteins, alongside regulators of intercellular signalling. General significance Comprising recently proposed targets to treat cancers, infections, metabolic disease and neurodegeneration, the advancement of TPC/TRPML understanding is of considerable importance. This review proposes novel directions elucidating TPC/TRPML relevance in health and disease. This article is part of a Special Issue entitled: ECS Meeting edited by Claus Heizmann, Joachim Krebs and Jacques Haiech.
-
Small Molecules for Early Endosome-Specific Patch Clamping
Chemistry & Biology, 2017Co-Authors: Chengchang Chen, Susan A. Slaugenhaupt, Martin Biel, Christian Wahl-schott, Stefan Heller, Yukai Chao, Lars Becker, Elisabeth Butz, Yulia Grishchuk, Christian GrimmAbstract:Summary To resolve the subcellular distribution of endolysosomal ion channels, we have established a novel experimental approach to selectively patch clamp Rab5 positive early endosomes (EE) versus Rab7/LAMP1-positive late endosomes/lysosomes (LE/LY). To functionally characterize ion channels in endolysosomal membranes with the patch-clamp technique, it is important to develop techniques to selectively enlarge the respective organelles. We found here that two small molecules, wortmannin and latrunculin B, enlarge Rab5-positive EE when combined but not Rab7-, LAMP1-, or Rab11 (RE)-positive vesicles. The two compounds act rapidly, specifically, and are readily applicable in contrast to genetic approaches or previously used compounds such as vacuolin, which enlarges EE, RE, and LE/LY. We apply this approach here to measure currents mediated by TRPML channels, in particular TRPML3, which we found to be functionally active in both EE and LE/LY in overexpressing cells as well as in endogenously expressing CD11b+ lung-tissue macrophages.
-
Endo-lysosomal TRP mucolipin-1 channels trigger global ER Ca2+ release and Ca2+ influx
Journal of Cell Science, 2016Co-Authors: Bethan S. Kilpatrick, Christian Grimm, Elizabeth Yates, Anthony H.v. Schapira, Sandip PatelAbstract:Transient receptor potential (TRP) mucolipins (TRPMLs), encoded by the MCOLN genes, are patho-physiologically relevant endo-lysosomal ion channels crucial for membrane trafficking. Several lines of evidence suggest that TRPMLs mediate localised Ca2+ release but their role in Ca2+ signalling is not clear. Here, we show that activation of endogenous and recombinant TRPMLs with synthetic agonists evoked global Ca2+ signals in human cells. These signals were blocked by a dominant-negative TRPML1 construct and a TRPML antagonist. We further show that, despite a predominant lysosomal localisation, TRPML1 supports both Ca2+ release and Ca2+ entry. Ca2+ release required lysosomal and ER Ca2+ stores suggesting that TRPMLs, like other endo-lysosomal Ca2+ channels, are capable of ‘chatter’ with ER Ca2+ channels. Our data identify new modalities for TRPML1 action.
-
TRPML channels and mucolipidosis type iv
2014Co-Authors: Christian Grimm, Math P. CuajungcoAbstract:The transient receptor potential (TRP) mucolipin channels TRPML1, TRPML2, and TRPML3 are non-selective cation channels predominantly found in the endolysosomal system. Mutations in the TRPML1 gene (also known as MCOLN1) cause mucolipidosis type IV in humans manifested by psychomotor abnormalities, corneal clouding, retinal degeneration, and progressive neurodegeneration. The recent identification of small compound chemical activators for TRPML channels has opened up the possibility to study TRPML mutant and wild-type isoforms both in vitro and in vivo in more detail. These compounds will permit further investigation on the functional roles of TRPML channels in the endolysosomal system. Ultimately, these drugs or their derivatives could be used to design selective pharmacological tools to gate and rescue specific loss-of-function point mutations in TRPML1 that cause mucolipidosis type IV. Recently discovered TRPML channel interaction partners may serve as alternative pharmacological targets for the treatment of mucolipidosis type IV.
Xinghua Feng - One of the best experts on this subject based on the ideXlab platform.
-
Targeting Sequence and Function-Dependence of Subcellular Localization of Transient Receptor Potential Mucolipin Channels
Biophysical Journal, 2016Co-Authors: Jian Xiong, Xinghua FengAbstract:Both of TRPML1 and TRPML3 are members of the mucolipin subfamily of Transient Receptor Potential (TRP) channels. They have been implicated in endolysosomal functions such as divalent cation release, luminal pH regulation and vesicle trafficking. Interestingly, whereas TRPML1 is almost extensively localized in lysosomes, TRPML3 is typically found in both lysosomes and the plasma membrane (PM). It has been shown that TRPML3 localization depends on TRPML1, but the mechanism remains unknown. Recently, a number of TRPML1 mutants have been reported to be either retained in the endoplasmic reticulum (ER) or preferentially targeted the PM. Coexpressing these mutants with either wild type TRPML3 or a non-functional ER-retained mutant, TRPML3-KK, we examined how differentially targeted TRPML1 proteins affect TRPML3 localization. We show that while the wild type TRPML1 decreased the PM targeting of TRPML3, the PM-targeted TRPML1 mutants did not enhance PM localization of TRPML3. Interestingly, not only the wild type TRPML1 brought TRPML3-KK to lysosomes, but also TRPML3 brought the ER-retained TRPML1-KK to these acidic organelles. Moreover, coexpression of TRPML-KK not only reduced TRPML3-mediated Ca2+ response to a TRPML agonist, but also nearly abolished PM localization of TRPML3. We conclude that while the lysosome targeting sequence(s) is important for sorting TRPML channels out of ER-Golgi network, the ion-conducting function may be critical for PM trafficking of these endolysosomal channels.
-
differential mechanisms of action of the mucolipin synthetic agonist ml sa1 on insect TRPML and mammalian TRPML1
Cell Calcium, 2014Co-Authors: Xinghua Feng, Yungang Lu, Jian XiongAbstract:Abstract Mucolipin synthetic agonist 1 (ML-SA1) was recently identified to activate mammalian TRPML channels and shown to alleviate lipid accumulation in lysosomes of cellular models of lysosome storage diseases, mucolipidosis type IV (MLIV) and Niemann–Pick's disease type C (NPC). Owning to its potential use in complimenting genetic studies in Drosophila melanogaster to elucidate the cellular and physiological functions of TRPML channels, we examined the effect of ML-SA1 on Drosophila TRPML expressed in HEK293 cells using whole-cell, inside-out, and whole-lysosome electrophysiological recordings. We previously showed that when expressed in HEK293 cells, Drosophila TRPML was localized and functional on both plasma membrane and endolysosome. We show here that in both inside-out patches excised from the plasma membrane and whole-lysosome recordings from enlarged endolysosome vacuoles, ML-SA1 failed to activate TRPML unless exogenous phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2] was applied. At 1 μM ML-SA1, the sensitivity of TRPML to PI(3,5)P2 increased approximately by 10-fold and at 10 μM ML-SA1, the deactivation of PI(3,5)P2-evoked TRPML currents was markedly slowed. On the other hand, constitutive activation of TRPML by a mutation that mimics the varitint-waddler (Va) mutation of mouse TRPML3 rendered the insect channel sensitive to activation by ML-SA1 alone. Moreover, different from the insect TRPML, mouse TRPML1 was readily activated by ML-SA1 independent of PI(3,5)P2. Thus, our data reveal that while ML-SA1 acts as a true agonist at mouse TRPML1, it behaves as an allosteric activator of the Drosophila TRPML, showing dependence on and the ability to stabilize open conformation of the insect channels.
-
drosophila TRPML forms pi 3 5 p2 activated cation channels in both endolysosomes and plasma membrane
Journal of Biological Chemistry, 2014Co-Authors: Xinghua Feng, Yu Huang, Yungang Lu, Jian Xiong, Chingon Wong, Pu Yang, De Chen, Guangwei Du, Kartik VenkatachalamAbstract:Transient Receptor Potential mucolipin (TRPML) channels are implicated in endolysosomal trafficking, lysosomal Ca2+ and Fe2+ release, lysosomal biogenesis, and autophagy. Mutations in human TRPML1 cause the lysosome storage disease, mucolipidosis type IV (MLIV). Unlike vertebrates, which express three TRPML genes, TRPML1–3, the Drosophila genome encodes a single TRPML gene. Although the TRPML-deficient flies exhibit cellular defects similar to those in mammalian TRPML1 mutants, the biophysical properties of Drosophila TRPML channel remained uncharacterized. Here, we show that transgenic expression of human TRPML1 in the neurons of Drosophila TRPML mutants partially suppressed the pupal lethality phenotype. When expressed in HEK293 cells, Drosophila TRPML was localized in both endolysosomes and plasma membrane and was activated by phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2) applied to the cytoplasmic side in whole lysosomes and inside-out patches excised from plasma membrane. The PI(3,5)P2-evoked currents were blocked by phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), but not other phosphoinositides. Using TRPML A487P, which mimics the varitint-waddler (Va) mutant of mouse TRPML3 with constitutive whole-cell currents, we show that TRPML is biphasically regulated by extracytosolic pH, with an optimal pH about 0.6 pH unit higher than that of human TRPML1. In addition to monovalent cations, TRPML exhibits high permeability to Ca2+, Mn2+, and Fe2+, but not Fe3+. The TRPML currents were inhibited by trivalent cations Fe3+, La3+, and Gd3+. These features resemble more closely to mammalian TRPML1 than TRPML2 and TRPML3, but with some obvious differences. Together, our data support the use of Drosophila for assessing functional significance of TRPML1 in cell physiology.
Yungang Lu - One of the best experts on this subject based on the ideXlab platform.
-
differential mechanisms of action of the mucolipin synthetic agonist ml sa1 on insect TRPML and mammalian TRPML1
Cell Calcium, 2014Co-Authors: Xinghua Feng, Yungang Lu, Jian XiongAbstract:Abstract Mucolipin synthetic agonist 1 (ML-SA1) was recently identified to activate mammalian TRPML channels and shown to alleviate lipid accumulation in lysosomes of cellular models of lysosome storage diseases, mucolipidosis type IV (MLIV) and Niemann–Pick's disease type C (NPC). Owning to its potential use in complimenting genetic studies in Drosophila melanogaster to elucidate the cellular and physiological functions of TRPML channels, we examined the effect of ML-SA1 on Drosophila TRPML expressed in HEK293 cells using whole-cell, inside-out, and whole-lysosome electrophysiological recordings. We previously showed that when expressed in HEK293 cells, Drosophila TRPML was localized and functional on both plasma membrane and endolysosome. We show here that in both inside-out patches excised from the plasma membrane and whole-lysosome recordings from enlarged endolysosome vacuoles, ML-SA1 failed to activate TRPML unless exogenous phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2] was applied. At 1 μM ML-SA1, the sensitivity of TRPML to PI(3,5)P2 increased approximately by 10-fold and at 10 μM ML-SA1, the deactivation of PI(3,5)P2-evoked TRPML currents was markedly slowed. On the other hand, constitutive activation of TRPML by a mutation that mimics the varitint-waddler (Va) mutation of mouse TRPML3 rendered the insect channel sensitive to activation by ML-SA1 alone. Moreover, different from the insect TRPML, mouse TRPML1 was readily activated by ML-SA1 independent of PI(3,5)P2. Thus, our data reveal that while ML-SA1 acts as a true agonist at mouse TRPML1, it behaves as an allosteric activator of the Drosophila TRPML, showing dependence on and the ability to stabilize open conformation of the insect channels.
-
drosophila TRPML forms pi 3 5 p2 activated cation channels in both endolysosomes and plasma membrane
Journal of Biological Chemistry, 2014Co-Authors: Xinghua Feng, Yu Huang, Yungang Lu, Jian Xiong, Chingon Wong, Pu Yang, De Chen, Guangwei Du, Kartik VenkatachalamAbstract:Transient Receptor Potential mucolipin (TRPML) channels are implicated in endolysosomal trafficking, lysosomal Ca2+ and Fe2+ release, lysosomal biogenesis, and autophagy. Mutations in human TRPML1 cause the lysosome storage disease, mucolipidosis type IV (MLIV). Unlike vertebrates, which express three TRPML genes, TRPML1–3, the Drosophila genome encodes a single TRPML gene. Although the TRPML-deficient flies exhibit cellular defects similar to those in mammalian TRPML1 mutants, the biophysical properties of Drosophila TRPML channel remained uncharacterized. Here, we show that transgenic expression of human TRPML1 in the neurons of Drosophila TRPML mutants partially suppressed the pupal lethality phenotype. When expressed in HEK293 cells, Drosophila TRPML was localized in both endolysosomes and plasma membrane and was activated by phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2) applied to the cytoplasmic side in whole lysosomes and inside-out patches excised from plasma membrane. The PI(3,5)P2-evoked currents were blocked by phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), but not other phosphoinositides. Using TRPML A487P, which mimics the varitint-waddler (Va) mutant of mouse TRPML3 with constitutive whole-cell currents, we show that TRPML is biphasically regulated by extracytosolic pH, with an optimal pH about 0.6 pH unit higher than that of human TRPML1. In addition to monovalent cations, TRPML exhibits high permeability to Ca2+, Mn2+, and Fe2+, but not Fe3+. The TRPML currents were inhibited by trivalent cations Fe3+, La3+, and Gd3+. These features resemble more closely to mammalian TRPML1 than TRPML2 and TRPML3, but with some obvious differences. Together, our data support the use of Drosophila for assessing functional significance of TRPML1 in cell physiology.
Bernd Nilius - One of the best experts on this subject based on the ideXlab platform.
-
On the Origin of Bladder Sensing: Tr(i)ps in Urology
Neurourology and Urodynamics, 2020Co-Authors: Wouter Everaerts, Thomas Gevaert, Bernd Nilius, Dirk De RidderAbstract:The mammalian TRP family consists of 28 channels that can be subdivided into 6 different classes: TRPV (vanilloid), TRPC (canonical), TRPM (Melastatin), TRPP (Polycystin), TRPML (Mucolipin), and TRPA (Ankyrin). TRP channels are activated by a diversity of physical (voltage, heat, cold, mechanical stress) or chemical (pH, osmolality) stimuli and by binding of specific ligands, enabling them to act as multifunctional sensors at the cellular level. Currently, a lot of scientific research is devoted to these channels and their role in sensing mechanisms throughout the body. In urology, there’s a growing conviction that disturbances in afferent (sensory) mechanisms are highly important in the pathogenesis of functional problems. Therefore, the TRP family forms an interesting new target to focus on. In this review we attempt to summarize the existing knowledge about TRP channels in the urogenital tract. So far, TRPV1, TRPV2, TRPV4, TRPM8, and TRPA1 have been described in different parts of the urogenital tract. Although only TRPV1 (the vanilloid receptor) has been extensively studied so far, more evidence is slowly accumulating about the role of other TRP channels in the (patho)physiology of the urogenital tract. Neurourol. Urodynam. 27:264–273, 2008. 2007 Wiley-Liss, Inc.
-
PRO T EIN FA MIL Y REVIEW
2020Co-Authors: Bernd Nilius, Grzegorz OwsianikAbstract:Summary The transient receptor potential (TRP) multigene superfamily encodes integral membrane proteins that function as ion channels. Members of this family are conserved in yeast, invertebrates and vertebrates. The TRP family is subdivided into seven subfamilies: TRPC (canonical), TRPV (vanilloid), TRPM (melastatin), TRPP (polycystin), TRPML (mucolipin), TRPA (ankyrin) and TRPN (NOMPC-like); the latter is found only in � �
-
P R O T E I N FA M I LY R E V I E W
2020Co-Authors: Bernd Nilius, Grzegorz OwsianikAbstract:Summary The transient receptor potential (TRP) multigene superfamily encodes integral membrane proteins that function as ion channels. Members of this family are conserved in yeast, invertebrates and vertebrates. The TRP family is subdivided into seven subfamilies: TRPC (canonical), TRPV (vanilloid), TRPM (melastatin), TRPP (polycystin), TRPML (mucolipin), TRPA (ankyrin) and TRPN (NOMPC-like); the latter is found only in invertebrates and fish. TRP ion channels are widely expressed in many different tissues and cell types, where they are involved in diverse physiological processes, such as sensation of different stimuli or ion homeostasis. Most TRPs are non-selective cation channels, only few are highly Ca 2+ selective, some are even permeable for highly hydrated Mg 2+ ions. This
-
TRP channels: an overview.
Cell calcium, 2020Co-Authors: Stine Falsig Pedersen, Grzegorz Owsianik, Bernd NiliusAbstract:The TRP ("transient receptor potential") family of ion channels now comprises more than 30 cation channels, most of which are permeable for Ca2+, and some also for Mg2+. On the basis of sequence homology, the TRP family can be divided in seven main subfamilies: the TRPC ('Canonical') family, the TRPV ('Vanilloid') family, the TRPM ('Melastatin') family, the TRPP ('Polycystin') family, the TRPML ('Mucolipin') family, the TRPA ('Ankyrin') family, and the TRPN ('NOMPC') family. The cloning and characterization of members of this cation channel family has exploded during recent years, leading to a plethora of data on the roles of TRPs in a variety of tissues and species, including mammals, insects, and yeast. The present review summarizes the most pertinent recent evidence regarding the structural and functional properties of TRP channels, focusing on the regulation and physiology of mammalian TRPs.
-
The Role of Transient Receptor Potential Cation Channels in Ca2þ Signaling
2020Co-Authors: Maarten Gees, Barbara Colsoul, Bernd NiliusAbstract:The 28 mammalian members of the super-family of transient receptor potential (TRP) channels are cation channels, mostly permeable to both monovalent and divalent cations, and can be subdivided into six main subfamilies: the TRPC (canonical), TRPV (vanilloid), TRPM (melastatin), TRPP (polycystin), TRPML (mucolipin), and the TRPA (ankyrin) groups. TRP channels are widely expressed in a large number of different tissues and cell types, and their biological roles appear to be equally diverse. In general, considered as polymodal cell sensors, they play a much more diverse role than anticipated. Functionally, TRP channels, when activated, cause cell depolarization, which may trigger a plethora of voltage-dependent ion channels. Upon stimulation, Ca2þ permeable TRP channels generate changes in the intracellular Ca2þ concentration, [Ca]i, by Ca 2þ entry via the plasma membrane. However, more and more evidence is arising that TRP channels are also located in intracellular organelles and serve as intracellular Ca2þ release channels. This review focuses on three major tasks of TRP channels: (1) the function of TRP channels as Ca2þ entry channels; (2) the electrogenic actions of TRPs; and (3) TRPs as Ca2þ release channels in intracellular organelles.