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Reversible intracellular translocation of KRas but not HRas in hippocampal neurons regulated by Ca(2+)/calmodulin

The Ras/MAPK pathway regulates synaptic plasticity and cell survival in neurons of the central nervous system. Here, we show that KRas, but not HRas, acutely translocates from the plasma membrane (PM) to the Golgi complex and early/recycling endosomes in response to neuronal activity. Translocation...

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Detalles Bibliográficos
Autores principales: Fivaz, Marc, Meyer, Tobias
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2005
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2171478/
https://www.ncbi.nlm.nih.gov/pubmed/16043511
http://dx.doi.org/10.1083/jcb.200409157
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author Fivaz, Marc
Meyer, Tobias
author_facet Fivaz, Marc
Meyer, Tobias
author_sort Fivaz, Marc
collection PubMed
description The Ras/MAPK pathway regulates synaptic plasticity and cell survival in neurons of the central nervous system. Here, we show that KRas, but not HRas, acutely translocates from the plasma membrane (PM) to the Golgi complex and early/recycling endosomes in response to neuronal activity. Translocation is reversible and mediated by the polybasic-prenyl membrane targeting motif of KRas. We provide evidence that KRas translocation occurs through sequestration of the polybasic-prenyl motif by Ca(2+)/calmodulin (Ca(2+)/CaM) and subsequent release of KRas from the PM, in a process reminiscent of GDP dissociation inhibitor–mediated membrane recycling of Rab and Rho GTPases. KRas translocation was accompanied by partial intracellular redistribution of its activity. We conclude that the polybasic-prenyl motif acts as a Ca(2+)/CaM-regulated molecular switch that controls PM concentration of KRas and redistributes its activity to internal sites. Our data thus define a novel signaling mechanism that differentially regulates KRas and HRas localization and activity in neurons.
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spelling pubmed-21714782008-03-05 Reversible intracellular translocation of KRas but not HRas in hippocampal neurons regulated by Ca(2+)/calmodulin Fivaz, Marc Meyer, Tobias J Cell Biol Research Articles The Ras/MAPK pathway regulates synaptic plasticity and cell survival in neurons of the central nervous system. Here, we show that KRas, but not HRas, acutely translocates from the plasma membrane (PM) to the Golgi complex and early/recycling endosomes in response to neuronal activity. Translocation is reversible and mediated by the polybasic-prenyl membrane targeting motif of KRas. We provide evidence that KRas translocation occurs through sequestration of the polybasic-prenyl motif by Ca(2+)/calmodulin (Ca(2+)/CaM) and subsequent release of KRas from the PM, in a process reminiscent of GDP dissociation inhibitor–mediated membrane recycling of Rab and Rho GTPases. KRas translocation was accompanied by partial intracellular redistribution of its activity. We conclude that the polybasic-prenyl motif acts as a Ca(2+)/CaM-regulated molecular switch that controls PM concentration of KRas and redistributes its activity to internal sites. Our data thus define a novel signaling mechanism that differentially regulates KRas and HRas localization and activity in neurons. The Rockefeller University Press 2005-08-01 /pmc/articles/PMC2171478/ /pubmed/16043511 http://dx.doi.org/10.1083/jcb.200409157 Text en Copyright © 2005, 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/).
spellingShingle Research Articles
Fivaz, Marc
Meyer, Tobias
Reversible intracellular translocation of KRas but not HRas in hippocampal neurons regulated by Ca(2+)/calmodulin
title Reversible intracellular translocation of KRas but not HRas in hippocampal neurons regulated by Ca(2+)/calmodulin
title_full Reversible intracellular translocation of KRas but not HRas in hippocampal neurons regulated by Ca(2+)/calmodulin
title_fullStr Reversible intracellular translocation of KRas but not HRas in hippocampal neurons regulated by Ca(2+)/calmodulin
title_full_unstemmed Reversible intracellular translocation of KRas but not HRas in hippocampal neurons regulated by Ca(2+)/calmodulin
title_short Reversible intracellular translocation of KRas but not HRas in hippocampal neurons regulated by Ca(2+)/calmodulin
title_sort reversible intracellular translocation of kras but not hras in hippocampal neurons regulated by ca(2+)/calmodulin
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2171478/
https://www.ncbi.nlm.nih.gov/pubmed/16043511
http://dx.doi.org/10.1083/jcb.200409157
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