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Dev Cell. 2015 Feb 9;32(3):318-34. doi: 10.1016/j.devcel.2014.12.019. Epub 2015 Jan 29.

Rac1 nucleocytoplasmic shuttling drives nuclear shape changes and tumor invasion.

Author information

1
Integrin Signaling Laboratory, Department of Vascular Biology and Inflammation, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Melchor Fernández Almagro 3, 28029 Madrid, Spain.
2
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.
3
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.
4
Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Tukholmankatu 8, P.O. Box 20, 00014 Helsinki, Finland.
5
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.
6
Proteomics Unit, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Melchor Fernández Almagro 3, 28029 Madrid, Spain.
7
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.

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.

PMID:
25640224
DOI:
10.1016/j.devcel.2014.12.019
[Indexed for MEDLINE]
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