Rac-ing to the plasma membrane: the long and complex work commute of Rac1 during cell signaling.
The functional cycle of the Rac1 GTPase involves a large number of steps, including post-translational processing, cytosolic sequestration by RhoGDIs, translocation to specific subcellular localizations, activation by GDP/GTP exchange, inactivation by GTP hydrolysis, and re-formation of cytosolic Rac1/RhoGDI inhibitory complexes. Here, we summarize the current knowledge about the regulation of those steps. In addition, we discuss a recently described, cytoskeletal-dependent feed-back loop that favors the efficient translocation and activation of Rac subfamily proteins during cell signaling. This route is mediated by a heteromolecular protein complex composed of the cytoskeletal protein coronin1A, the Dbl family member ArhGEF7, the serine/threonine kinase Pak1, and the Rac1/RhoGDI dimer. This route promotes the translocation of Rac1/RhoGDI to F-actin-rich juxtamembrane areas, the Pak1-dependent release of Rac1 from the Rac1/RhoGDI complex, and Rac1 activation. This pathway is important for optimal Rac1 activation during the signaling of the EGF receptor, integrins, and the antigenic T-cell receptor.
Centro de Investigación del Cáncer, Instituto de Biología Molecular y Celular del Cáncer, CSIC-University of Salamanca, Campus Unamuno, Salamanca, Spain. xbustelo@usal.es
Xosé R
XR
Bustelo
Virginia
V
Ojeda
María
M
Barreira
Vincent
V
Sauzeau
Antonio
A
Castro-Castro
D000818:Animals; D003599:Cytoskeleton / Q000378:metabolism*; D005786:Gene Expression Regulation; D008840:Microfilament Proteins / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*
D008840:Microfilament Proteins; D020830:rac1 GTP-Binding Protein