Document Detail


Galpha(13) mediates activation of a depolarizing chloride current that accompanies RhoA activation in both neuronal and nonneuronal cells.
MedLine Citation:
PMID:  11231129     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Loss of membrane potential (membrane depolarization) is one of the earliest and most striking responses of quiescent cells to stimulation with serum or G protein-coupled receptor (GPCR) agonists such as lysophosphatidic acid and thrombin. Membrane depolarization is due to the activation of a chloride conductance. While this response has received relatively little attention in the past, it is clear that the acute loss of membrane potential may have important physiological consequences. However, the dissection of the underlying G protein pathway and the establishment of cause-effect relationships have remained elusive to date. Here we report that, in neuronal cells, the depolarizing chloride current invariably accompanies GPCR-induced activation of RhoA and subsequent neurite retraction, and neither of these events requires phosphoinositide hydrolysis or Ca2+ mobilization. Through antibody microinjections and a genetic approach, we demonstrate that activation of the chloride conductance is mediated by Galpha(13) in a RhoA-independent manner in both neuronal cells and fibroblasts. We further show that, in neuronal cells, this newly described Galpha(13) pathway may profoundly modulate membrane excitability during RhoA-regulated neurite remodeling.
Authors:
F R Postma; K Jalink; T Hengeveld; S Offermanns; W H Moolenaar
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Current biology : CB     Volume:  11     ISSN:  0960-9822     ISO Abbreviation:  Curr. Biol.     Publication Date:  2001 Jan 
Date Detail:
Created Date:  2001-03-20     Completed Date:  2001-06-07     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9107782     Medline TA:  Curr Biol     Country:  England    
Other Details:
Languages:  eng     Pagination:  121-4     Citation Subset:  IM    
Affiliation:
Division of Cellular Biochemistry, The Netherlands Cancer Institute and Centre for Biomedical Genetics, Amsterdam 1066 CX, The Netherlands.
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MeSH Terms
Descriptor/Qualifier:
Action Potentials
Animals
Cell Line
Chloride Channels / metabolism*
DNA-Binding Proteins / physiology*
GTP-Binding Protein alpha Subunits, G12-G13
Neurons / metabolism*,  physiology
rhoA GTP-Binding Protein / metabolism*
Chemical
Reg. No./Substance:
0/Chloride Channels; 0/DNA-Binding Proteins; EC 3.6.5.1/GTP-Binding Protein alpha Subunits, G12-G13; EC 3.6.5.2/rhoA GTP-Binding Protein

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