title: Rac1 nucleocytoplasmic shuttling drives nuclear shape changes and tumor invasion.
abstract: Nuclear membrane microdomains are proposed to act as platforms for regulation of nuclear function, but little is known about the mechanisms controlling their formation. Organization of the plasma membrane is regulated by actin polymerization, and the existence of an actin pool in the nucleus suggests that a similar mechanism might operate here. We show that nuclear membrane organization and morphology are regulated by the nuclear level of active Rac1 through actin polymerization-dependent mechanisms. Rac1 nuclear export is mediated by two internal nuclear export signals and through its interaction with nucleophosmin-1 (B23), which acts as a Rac1 chaperone inside the nucleus. Rac1 nuclear accumulation alters the balance between cytosolic Rac1 and Rho, increasing RhoA signaling in the cytoplasm and promoting a highly invasive phenotype. Nuclear Rac1 shuttling is a finely tuned mechanism for controlling nuclear shape and organization and cell invasiveness.
authors: Integrin Signaling Laboratory, Department of Vascular Biology and Inflammation, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Melchor Fernández Almagro 3, 28029 Madrid, Spain.
authors: Inmaculada
authors: I
authors: Navarro-Lérida
authors: Integrin Signaling Laboratory, Department of Vascular Biology and Inflammation, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Melchor Fernández Almagro 3, 28029 Madrid, Spain; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Tukholmankatu 8, P.O. Box 20, 00014 Helsinki, Finland.
authors: Teijo
authors: T
authors: Pellinen
authors: Microscopy and Dynamic Imaging Unit, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Melchor Fernández Almagro 3, 28029 Madrid, Spain; Facultad de Ciencias Químicas, Universidad de Concepción, 4070371 Concepción, Chile.
authors: Susana A
authors: SA
authors: Sanchez
authors: Integrin Signaling Laboratory, Department of Vascular Biology and Inflammation, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Melchor Fernández Almagro 3, 28029 Madrid, Spain.
authors: Marta C
authors: MC
authors: Guadamillas
authors: Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Tukholmankatu 8, P.O. Box 20, 00014 Helsinki, Finland.
authors: Yinhai
authors: Y
authors: Wang
authors: Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Tukholmankatu 8, P.O. Box 20, 00014 Helsinki, Finland; HUSLAB, Department of Pathology, Haartman Institute, Helsinki University Central Hospital, Haartmaninkatu 3 C, P.O. Box 400, 00029 HUS Helsinki, Finland.
authors: Tuomas
authors: T
authors: Mirtti
authors: Proteomics Unit, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Melchor Fernández Almagro 3, 28029 Madrid, Spain.
authors: Enrique
authors: E
authors: Calvo
authors: Integrin Signaling Laboratory, Department of Vascular Biology and Inflammation, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Melchor Fernández Almagro 3, 28029 Madrid, Spain. Electronic address: madelpozo@cnic.es.
authors: Miguel A
authors: MA
authors: Del Pozo
mesh_terms: D000199:Actins / Q000378:metabolism*; D021581:Active Transport, Cell Nucleus; D002462:Cell Membrane / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism*; D006801:Humans; D009361:Neoplasm Invasiveness; D009687:Nuclear Proteins / Q000378:metabolism; D000090243:Nucleophosmin; D015398:Signal Transduction / Q000502:physiology; D020830:rac1 GTP-Binding Protein / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D000199:Actins; C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin; D020830:rac1 GTP-Binding Protein; D020742:rhoA GTP-Binding Protein