Cell cycle– and swelling-induced activation of a Caenorhabditis elegans ClC channel is mediated by CeGLC-7α/β phosphatases

ClC voltage-gated anion channels have been identified in bacteria, yeast, plants, and animals. The biophysical and structural properties of ClCs have been studied extensively, but relatively little is known about their precise physiological functions. Furthermore, virtually nothing is known about th...

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Main Authors:	Rutledge, Eric, Denton, Jerod, Strange, Kevin
Format:	Online
Language:	English
Published:	The Rockefeller University Press 2002
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2173826/

id	pubmed-2173826
recordtype	oai_dc
spelling	pubmed-21738262008-05-01 Cell cycle– and swelling-induced activation of a Caenorhabditis elegans ClC channel is mediated by CeGLC-7α/β phosphatases Rutledge, Eric Denton, Jerod Strange, Kevin Report ClC voltage-gated anion channels have been identified in bacteria, yeast, plants, and animals. The biophysical and structural properties of ClCs have been studied extensively, but relatively little is known about their precise physiological functions. Furthermore, virtually nothing is known about the signaling pathways and molecular mechanisms that regulate channel activity. The nematode Caenorhabditis elegans provides significant experimental advantages for characterizing ion channel function and regulation. We have shown previously that the ClC Cl− channel homologue CLH-3 is expressed in C. elegans oocytes, and that it is activated during meiotic maturation and by cell swelling. We demonstrate here that depletion of intracellular ATP or removal of Mg2+, experimental maneuvers that inhibit kinase function, constitutively activate CLH-3. Maturation- and swelling-induced channel activation are inhibited by type 1 serine/threonine phosphatase inhibitors. RNA interference studies demonstrated that the type 1 protein phosphatases CeGLC-7α and β, both of which play essential regulatory roles in mitotic and meiotic cell cycle events, mediate CLH-3 activation. We have suggested previously that CLH-3 and mammalian ClC-2 are orthologues that play important roles in heterologous cell–cell interactions, intercellular communication, and regulation of cell cycle–dependent physiological processes. Consistent with this hypothesis, we show that heterologously expressed rat ClC-2 is also activated by serine/threonine dephosphorylation, suggesting that the two channels have common regulatory mechanisms. The Rockefeller University Press 2002-08-05 /pmc/articles/PMC2173826/ /pubmed/12163466 http://dx.doi.org/10.1083/jcb.200204142 Text en Copyright © 2002, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Rutledge, Eric Denton, Jerod Strange, Kevin
spellingShingle	Rutledge, Eric Denton, Jerod Strange, Kevin Cell cycle– and swelling-induced activation of a Caenorhabditis elegans ClC channel is mediated by CeGLC-7α/β phosphatases
author_facet	Rutledge, Eric Denton, Jerod Strange, Kevin
author_sort	Rutledge, Eric
title	Cell cycle– and swelling-induced activation of a Caenorhabditis elegans ClC channel is mediated by CeGLC-7α/β phosphatases
title_short	Cell cycle– and swelling-induced activation of a Caenorhabditis elegans ClC channel is mediated by CeGLC-7α/β phosphatases
title_full	Cell cycle– and swelling-induced activation of a Caenorhabditis elegans ClC channel is mediated by CeGLC-7α/β phosphatases
title_fullStr	Cell cycle– and swelling-induced activation of a Caenorhabditis elegans ClC channel is mediated by CeGLC-7α/β phosphatases
title_full_unstemmed	Cell cycle– and swelling-induced activation of a Caenorhabditis elegans ClC channel is mediated by CeGLC-7α/β phosphatases
title_sort	cell cycle– and swelling-induced activation of a caenorhabditis elegans clc channel is mediated by ceglc-7α/β phosphatases
description	ClC voltage-gated anion channels have been identified in bacteria, yeast, plants, and animals. The biophysical and structural properties of ClCs have been studied extensively, but relatively little is known about their precise physiological functions. Furthermore, virtually nothing is known about the signaling pathways and molecular mechanisms that regulate channel activity. The nematode Caenorhabditis elegans provides significant experimental advantages for characterizing ion channel function and regulation. We have shown previously that the ClC Cl− channel homologue CLH-3 is expressed in C. elegans oocytes, and that it is activated during meiotic maturation and by cell swelling. We demonstrate here that depletion of intracellular ATP or removal of Mg2+, experimental maneuvers that inhibit kinase function, constitutively activate CLH-3. Maturation- and swelling-induced channel activation are inhibited by type 1 serine/threonine phosphatase inhibitors. RNA interference studies demonstrated that the type 1 protein phosphatases CeGLC-7α and β, both of which play essential regulatory roles in mitotic and meiotic cell cycle events, mediate CLH-3 activation. We have suggested previously that CLH-3 and mammalian ClC-2 are orthologues that play important roles in heterologous cell–cell interactions, intercellular communication, and regulation of cell cycle–dependent physiological processes. Consistent with this hypothesis, we show that heterologously expressed rat ClC-2 is also activated by serine/threonine dephosphorylation, suggesting that the two channels have common regulatory mechanisms.
publisher	The Rockefeller University Press
publishDate	2002
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2173826/
_version_	1611425421792903168

Cell cycle– and swelling-induced activation of a Caenorhabditis elegans ClC channel is mediated by CeGLC-7α/β phosphatases

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