title: Timing is everything: Rac1 controls Net1A localization to regulate cell adhesion.
abstract: Cell adhesion to the extracellular matrix elicits a temporal reorganization of the actin cytoskeleton that is regulated first by Rac1 and later by RhoA. The signaling mechanisms controlling late stage RhoA activation are incompletely understood. Net1A is a RhoA/RhoB-specific guanine nucleotide exchange factor that is required for cancer cell motility. The ability of Net1A to stimulate RhoA activation is negatively regulated by nuclear sequestration. However, mechanisms controlling the plasma membrane localization of Net1A had not previously been reported. Recently we have shown that Rac1 activation stimulates plasma membrane relocalization and activation of Net1A. Net1A relocalization is independent of its catalytic activity and does not require its C-terminal pleckstrin homology or PDZ interacting domains. Rac1 activation during cell adhesion stimulates a transient relocalization of Net1A that is terminated by proteasomal degradation of Net1A. Importantly, plasma membrane localization of Net1A is required for efficient myosin light chain phosphorylation, focal adhesion maturation, and cell spreading. These data show for the first time a physiological mechanism controlling Net1A relocalization from the nucleus. They also demonstrate a previously unrecognized role for Net1A in controlling actomyosin contractility and focal adhesion dynamics during cell adhesion.
authors.affiliation: Department of Integrative Biology and Pharmacology; University of Texas Health Science Center at Houston; Houston, TX USA.
authors.forename: Heather S
authors.initials: HS
authors.lastname: Carr
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Frost
mesh_terms: D000818:Animals; D002465:Cell Movement; D005260:Female; D022001:Focal Adhesions / Q000378:metabolism*; D006801:Humans; D015513:Oncogene Proteins / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*
chemical_list: D015513:Oncogene Proteins; D020830:rac1 GTP-Binding Protein
keywords: Net1A; Rac1; RhoA; breast cancer; cell adhesion; focal adhesion