The <i>Xenopus</i> TRPV6 homolog encodes a Mg<sup>2+</sup>‐permeant channel that is inhibited by interaction with TRPC1

Courjaret, Raphael Jean; Hubrack, Satanay; Daalis, Arwa; Dib, Maya; Machaca, Khaled

doi:10.1002/jcp.24411

Cited by 12 publications

(10 citation statements)

References 84 publications

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“…We measured steady-state currents at 250 mV induced by the addition of 5 mM extracellular Ca 2+ , which follows a large, transient Cl 2 current, mediated by native Ca 2+ -activated Cl 2 channels ( Fig. 1B), as described before (37,39). We indeed found that, compared with wild-type (WT) TRPV6, mutants A616N and M617N exhibited drastic 211 6 22-and 174 6 19-fold increases, respectively, in the channel activity, whereas other mutant channels behaved like WT or had lower activities ( Fig.…”

Section: Trpv6 and Trpv5 Gate Residuesmentioning

confidence: 99%

Identification and characterization of hydrophobic gate residues in TRP channels

Zheng

Cai

et al. 2018

FASEB j.

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Transient receptor potential (TRP) channels, subdivided into 6 subfamilies in mammals, have essential roles in sensory physiology. They respond to remarkably diverse stimuli, comprising thermal, chemical, and mechanical modalities, through opening or closing of channel gates. In this study, we systematically substituted the hydrophobic residues within the distal fragment of pore-lining helix S6 with hydrophilic residues and, based on Xenopus oocyte and mammalian cell electrophysiology and a hydrophobic gate theory, identified hydrophobic gates in TRPV6/V5/V4/C4/M8. We found that channel activity drastically increased when TRPV6 or TRPV5, but not any of their adjacent residues, was substituted with hydrophilic residues. Channel activity strongly correlated with the hydrophilicity of the residues at those sites, suggesting that consecutive hydrophobic residues TRPV6 and TRPV5 form a double-residue gate in each channel. By the same strategy, we identified a hydrophobic single-residue gate in TRPV4, TRPC4, and TRPM8. In support of the hydrophobic gate theory, hydrophilic substitution at the gate site, which removes the hydrophobic gate seal, substantially increased the activity of TRP channels in low-activity states but had little effect on the function of activated channels. The double-residue gate channels were more sensitive to small changes in the gate's hydrophobicity or size than single-residue gate channels. The unconventional double-reside gating mechanism in TRP channels may have been evolved to respond especially to physiologic stimuli that trigger relatively small gate conformational changes.-Zheng, W., Hu, R., Cai, R., Hofmann, L., Hu, Q., Fatehi, M., Long, W., Kong, T., Tang, J., Light, P., Flockerzi, V., Cao, Y., Chen, X.-Z. Identification and characterization of hydrophobic gate residues in TRP channels.

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Section: Trpv6 and Trpv5 Gate Residuesmentioning

confidence: 99%

Identification and characterization of hydrophobic gate residues in TRP channels

Zheng

Cai

et al. 2018

FASEB j.

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“…The mechanism by which TRPC1 suppressed TRPV6-mediated currents was through the sequestration of TRPV6 inside the cell and away from the plasma membrane (Schindl et al 2012). However, TRPC1 suppressed TRPV6 activity in Xenopus laevis oocytes by a mechanism different than cytosolic sequestration, as TRPV6 was detected in the plasma membrane of frog oocytes in the presence of TRPC1 (Courjaret et al 2013). It was suggested that the mechanism of TRPC1-mediated inhibition of TRPV6 might be species-specific.…”

Section: Trpv6mentioning

confidence: 95%

“…Nevertheless, understanding the mechanism(s) responsible for the negative regulation of TRPV6 is important in deciphering the molecular function of endogenous TRPV6, whose activity at the endogenous level is still elusive. Based on these results, it is conceivable that native TRPV6 is under negative regulation by TRPC1 and mechanisms that downregulate TRPC1 may represent modes of TRPV6 activation (Courjaret et al 2013). In this regard, Trpc1 knockout mice should be helpful in delineating endogenous TRPV6-mediated currents and cellular function(s).…”

Section: Trpv6mentioning

confidence: 96%

Trpc1

Nesin

Tsiokas

2014

Handbook of Experimental Pharmacology

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The TRPC1 ion channel was the first mammalian TRP channel to be cloned. In humans, it is encoded by the TRPC1 gene located in chromosome 3. The protein is predicted to consist of six transmembrane segments with the N- and C-termini located in the cytoplasm. The extracellular loop connecting transmembrane segments 5 and 6 participates in the formation of the ionic pore region. Inside the cell, TRPC1 is present in the endoplasmic reticulum, plasma membrane, intracellular vesicles, and primary cilium, an antenna-like sensory organelle functioning as a signaling platform. In human and rodent tissues, it shows an almost ubiquitous expression. TRPC1 interacts with a diverse group of proteins including ion channel subunits, receptors, and cytosolic proteins to mediate its effect on Ca(2+) signaling. It primarily functions as a cation nonselective channel within pathways controlling Ca(2+) entry in response to cell surface receptor activation. Through these pathways, it affects basic cell functions, such as proliferation and survival, differentiation, secretion, and cell migration, as well as cell type-specific functions such as chemotropic turning of neuronal growth cones and myoblast fusion. The biological role of TRPC1 has been studied in genetically engineered mice where the Trpc1 gene has been experimentally ablated. Although these mice live to adulthood, they show defects in several organs and tissues, such as the cardiovascular, central nervous, skeletal and muscular, and immune systems. Genetic and functional studies have implicated TRPC1 in diabetic nephropathy, Parkinson's disease, Huntington's disease, Duchenne muscular dystrophy, cancer, seizures, and Darier-White skin disease.

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“…After the washing steps, the proteins were eluted with the denaturing elution buffer provided in the kit. Western blotting was performed as previously described (Courjaret et al, 2013) and repeated three times on different samples. The anti-Ano1 antibody was used at a dilution of 1:1000 (SAB2102460, QC13356 Sigma).…”

Section: Immunoprecipitation and Western Blotmentioning

confidence: 99%

The Ca2+-activated Cl− channel Ano1 controls microvilli length and membrane surface area in the oocyte

Courjaret

Hodeify

Hubrack

et al. 2016

Journal of Cell Science

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Ca2+ -activated Cl − channels (CaCCs) play important physiological functions in epithelia and other tissues. In frog oocytes the CaCC Ano1 regulates resting membrane potential and the block to polyspermy. Here, we show that Ano1 expression increases the oocyte surface, revealing a novel function for Ano1 in regulating cell morphology. Confocal imaging shows that Ano1 increases microvilli length, which requires ERM-protein-dependent linkage to the cytoskeleton. A dominant-negative form of the ERM protein moesin precludes the Ano1-dependent increase in membrane area. Furthermore, both full-length and the truncated dominant-negative forms of moesin co-localize with Ano1 to the microvilli, and the two proteins co-immunoprecipitate. The Ano1-moesin interaction limits Ano1 lateral membrane mobility and contributes to microvilli scaffolding, therefore stabilizing larger membrane structures. Collectively, these results reveal a newly identified role for Ano1 in shaping the plasma membrane during oogenesis, with broad implications for the regulation of microvilli in epithelia.

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The Xenopus TRPV6 homolog encodes a Mg²⁺‐permeant channel that is inhibited by interaction with TRPC1

Cited by 12 publications

References 84 publications

Identification and characterization of hydrophobic gate residues in TRP channels

Identification and characterization of hydrophobic gate residues in TRP channels

Trpc1

The Ca2+-activated Cl− channel Ano1 controls microvilli length and membrane surface area in the oocyte

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The Xenopus TRPV6 homolog encodes a Mg2+‐permeant channel that is inhibited by interaction with TRPC1

Cited by 12 publications

References 84 publications

Identification and characterization of hydrophobic gate residues in TRP channels

Identification and characterization of hydrophobic gate residues in TRP channels

Trpc1

The Ca2+-activated Cl− channel Ano1 controls microvilli length and membrane surface area in the oocyte

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The Xenopus TRPV6 homolog encodes a Mg²⁺‐permeant channel that is inhibited by interaction with TRPC1