The F-BAR domain protein PACSIN2 associates with Rac1 and regulates cell spreading and migration.
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de Kreuk BJ, Nethe M, Fernandez-Borja M, Anthony EC, Hensbergen PJ, Deelder AM, Plomann M, Hordijk PL
The F-BAR domain protein PACSIN2 associates with Rac1 and regulates cell spreading and migration.
J Cell Sci. 2011 Jul 15;124(Pt 14):2375-88. doi: 10.1242/jcs.080630. Epub 2011 Jun 21.
- PubMed ID
- 21693584 [ View in PubMed]
- Abstract
The Rac1 GTPase controls cytoskeletal dynamics and is a key regulator of cell spreading and migration mediated by signaling through effector proteins, such as the PAK kinases and the Scar and WAVE proteins. We previously identified a series of regulatory proteins that associate with Rac1 through its hypervariable C-terminal domain, including the Rac1 activator beta-Pix (also known as Rho guanine-nucleotide-exchange factor 7) and the membrane adapter caveolin-1. Here, we show that Rac1 associates, through its C-terminus, with the F-BAR domain protein PACSIN2, an inducer of membrane tubulation and a regulator of endocytosis. We show that Rac1 localizes with PACSIN2 at intracellular tubular structures and on early endosomes. Active Rac1 induces a loss of PACSIN2-positive tubular structures. By contrast, Rac1 inhibition results in an accumulation of PACSIN2-positive tubules. In addition, PACSIN2 appears to regulate Rac1 signaling; siRNA-mediated loss of PACSIN2 increases the levels of Rac1-GTP and promotes cell spreading and migration in a wound healing assay. Moreover, ectopic expression of PACSIN2 reduces Rac1-GTP levels in a fashion that is dependent on the PACSIN2-Rac1 interaction, on the membrane-tubulating capacity of PACSIN2 and on dynamin. These data identify the BAR-domain protein PACSIN2 as a Rac1 interactor that regulates Rac1-mediated cell spreading and migration.