Coronin 1A promotes a cytoskeletal-based feedback loop that facilitates Rac1 translocation and activation |
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Authors: | Castro-Castro Antonio Ojeda Virginia Barreira María Sauzeau Vincent Navarro-Lérida Inmaculada Muriel Olivia Couceiro José R Pimentel-Muíños Felipe X Del Pozo Miguel A Bustelo Xosé R |
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Institution: | Centro de Investigación del Cáncer, CSIC-Salamanca University, Campus Unamuno s/n, Salamanca, Spain. |
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Abstract: | The activation of the Rac1 GTPase during cell signalling entails its translocation from the cytosol to membranes, release from sequestering Rho GDP dissociation inhibitors (RhoGDI), and GDP/GTP exchange. In addition to those steps, we show here that optimal Rac1 activation during cell signalling requires the engagement of a downstream, cytoskeletal-based feedback loop nucleated around the cytoskeletal protein coronin 1A and the Rac1 exchange factor ArhGEF7. These two proteins form a cytosolic complex that, upon Rac1-driven F-actin polymerization, translocates to juxtamembrane areas where it expands the pool of activated, membrane-bound Rac1. Such activity requires the formation of an F-actin/ArhGEF7-dependent physical complex of coronin 1A with Pak1 and RhoGDIα that, once assembled, promotes the Pak1-dependent dissociation of Rac1 from the Rac1/RhoGDIα complex and subsequent Rac1 activation. Genetic evidence demonstrates that this relay circuit is essential for generating sustained Rac1 activation levels during cell signalling. |
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Keywords: | ArhGEF7 F‐actin Pak RhoGDI Rho/Rac GTPases |
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