title: Coronin1 proteins dictate rac1 intracellular dynamics and cytoskeletal output.
abstract: Rac1 regulates lamellipodium formation, myosin II-dependent contractility, and focal adhesions during cell migration. While the spatiotemporal assembly of those processes is well characterized, the signaling mechanisms involved remain obscure. We report here that the cytoskeleton-related Coronin1A and -1B proteins control a myosin II inactivation-dependent step that dictates the intracellular dynamics and cytoskeletal output of active Rac1. This step is signaling-branch specific, since it affects the functional competence of active Rac1 only when forming complexes with downstream ArhGEF7 and Pak proteins in actomyosin-rich structures. The pathway is used by default unless Rac1 is actively rerouted away from the structures by upstream activators and signals from other Rho GTPases. These results indicate that Coronin1 proteins are at the center of a regulatory hub that coordinates Rac1 activation, effector exchange, and the F-actin organization state during cell signaling. Targeting this route could be useful to hamper migration of cancer cells harboring oncogenic RAC1 mutations.
authors: Centro de Investigación del Cáncer, Consejo Superior de Investigaciones Científicas (CSIC) and University of Salamanca, Campus Unamuno, Salamanca, Spain Instituto de Biología Molecular y Celular del Cáncer, Consejo Superior de Investigaciones Científicas (CSIC) and University of Salamanca, Campus Unamuno, Salamanca, Spain.
authors: Virginia
authors: V
authors: Ojeda
authors: Centro de Investigación del Cáncer, Consejo Superior de Investigaciones Científicas (CSIC) and University of Salamanca, Campus Unamuno, Salamanca, Spain Instituto de Biología Molecular y Celular del Cáncer, Consejo Superior de Investigaciones Científicas (CSIC) and University of Salamanca, Campus Unamuno, Salamanca, Spain.
authors: Antonio
authors: A
authors: Castro-Castro
authors: Centro de Investigación del Cáncer, Consejo Superior de Investigaciones Científicas (CSIC) and University of Salamanca, Campus Unamuno, Salamanca, Spain Instituto de Biología Molecular y Celular del Cáncer, Consejo Superior de Investigaciones Científicas (CSIC) and University of Salamanca, Campus Unamuno, Salamanca, Spain xbustelo@usal.es.
authors: Xosé R
authors: http://orcid.org/0000-0001-9398-6072
authors: XR
authors: Bustelo
mesh_terms: D000199:Actins / Q000378:metabolism; D000205:Actomyosin / Q000378:metabolism; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D003599:Cytoskeleton / Q000378:metabolism*; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D019169:Jurkat Cells; D008840:Microfilament Proteins / Q000378:metabolism*; D024462:Myosin Type II / Q000378:metabolism; D064067:Rho Guanine Nucleotide Exchange Factors / Q000378:metabolism; D015398:Signal Transduction; D054462:p21-Activated Kinases / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000235:genetics* / Q000378:metabolism*
chemical_list: D000199:Actins; D008840:Microfilament Proteins; D064067:Rho Guanine Nucleotide Exchange Factors; C072061:coronin proteins; D000205:Actomyosin; D054462:p21-Activated Kinases; D024462:Myosin Type II; D020830:rac1 GTP-Binding Protein