title: Coronin 1A promotes a cytoskeletal-based feedback loop that facilitates Rac1 translocation and activation.
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.
authors.affiliation: Centro de Investigación del Cáncer, CSIC-Salamanca University, Campus Unamuno s/n, Salamanca, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Castro-Castro
authors.forename: Virginia
authors.initials: V
authors.lastname: Ojeda
authors.forename: María
authors.initials: M
authors.lastname: Barreira
authors.forename: Vincent
authors.initials: V
authors.lastname: Sauzeau
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Navarro-Lérida
authors.forename: Olivia
authors.initials: O
authors.lastname: Muriel
authors.forename: José R
authors.initials: JR
authors.lastname: Couceiro
authors.forename: Felipe X
authors.initials: FX
authors.lastname: Pimentel-Muíños
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Del Pozo
authors.forename: Xosé R
authors.initials: XR
authors.lastname: Bustelo
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D003599:Cytoskeleton / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D005786:Gene Expression Regulation; D049452:Green Fluorescent Proteins / Q000378:metabolism; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000378:metabolism; D007700:Kinetics; D008840:Microfilament Proteins / Q000378:metabolism*; D008954:Models, Biological; D021381:Protein Transport; D015398:Signal Transduction; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*; D062948:rho Guanine Nucleotide Dissociation Inhibitor alpha; D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors
chemical_list: C569638:ARHGDIA protein, human; D000199:Actins; D020730:Guanine Nucleotide Dissociation Inhibitors; D008840:Microfilament Proteins; C107953:RAC1 protein, human; D062948:rho Guanine Nucleotide Dissociation Inhibitor alpha; D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors; C072061:coronin proteins; D049452:Green Fluorescent Proteins; D020830:rac1 GTP-Binding Protein