Gα13 mediates activation of a depolarizing chloride current that accompanies RhoA activation in both neuronal and nonneuronal cells
| Autor: | Kees Jalink, Trudi Hengeveld, Stefan Offermanns, Friso R. Postma, Wouter H. Moolenaar |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Neurons
Membrane potential RHOA Agricultural and Biological Sciences(all) Neurite biology Biochemistry Genetics and Molecular Biology(all) G protein Action Potentials Depolarization Stimulation GTP-Binding Protein alpha Subunits G12-G13 General Biochemistry Genetics and Molecular Biology Cell Line Cell biology DNA-Binding Proteins chemistry.chemical_compound chemistry Chloride Channels Lysophosphatidic acid biology.protein Animals rhoA GTP-Binding Protein General Agricultural and Biological Sciences G protein-coupled receptor |
| Zdroj: | Current Biology. 11:121-124 |
| ISSN: | 0960-9822 |
| DOI: | 10.1016/s0960-9822(01)00030-6 |
| Popis: | 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 [1–3]. Membrane depolarization is due to the activation of a chloride conductance [3]. 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 [4–6]. 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 Gα13 in a RhoA-independent manner in both neuronal cells and fibroblasts. We further show that, in neuronal cells, this newly described Gα13 pathway may profoundly modulate membrane excitability during RhoA-regulated neurite remodeling. |
| Databáze: | OpenAIRE |
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