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Cell Calcium. 2017 May;63:24-28. doi: 10.1016/j.ceca.2016.10.003. Epub 2016 Oct 28.

A conserved gating element in TRPV6 channels.

Author information

1
Experimentelle und Klinische Pharmakologie und Toxikologie, Universit├Ąt des Saarlandes, 66421 Homburg, Germany.
2
Experimentelle und Klinische Pharmakologie und Toxikologie, Universit├Ąt des Saarlandes, 66421 Homburg, Germany. Electronic address: Veit.Flockerzi@uks.eu.

Abstract

The Ca2+-selective tetrameric Transient Receptor Potential Vanilloid 6 (TRPV6) channel is an inwardly rectifying ion channel. The constitutive current endures Ca2+-induced inactivation as a result of the activation of phospholipase C followed depletion of phosphatidylinositol 4,5-bisphosphate, and calmodulin binding. Replacing a glycine residue within the cytosolic S4-S5 linker of the human TRPV6 protein, glycine 516, which is conserved in all TRP channel proteins, by a serine residue forces the channels into an open conformation thereby enhancing constitutive Ca2+ entry and preventing inactivation. Introduction of a second mutation (T621A) into TRPV6G516S reduces constitutive activity and partially rescues the TRPV6 function. According to the recently revealed crystal structure of the rat TRPV6 the T621 is adjacent to the distal end of the transmembrane segment 6 (S6) within a short linker between S6 and the helix formed by the TRP domain. These results indicate that the S4-S5 linker and the S6-TRP-domain linker are critical constituents of TRPV6 channel gating and that disturbance of their sequences foster constitutive Ca2+ entry.

KEYWORDS:

Calcium influx; Channel gating; Ion channel; Signal transduction; TRPV6; Transient receptor potential

PMID:
28029385
DOI:
10.1016/j.ceca.2016.10.003
[Indexed for MEDLINE]

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