The F-BAR domain protein PACSIN2 associates with Rac1 and regulates cell spreading and migration

Bart Jan de Kreuk, Micha Nethe, Mar Fernandez-Borja, Eloise C. Anthony, Paul J. Hensbergen, Andre M. Deelder, Markus Plomann, Peter L. Hordijk*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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 β-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.

Original languageEnglish
Pages (from-to)2375-2388
Number of pages14
JournalJournal of Cell Science
Volume124
Issue number14
DOIs
Publication statusPublished - 15 Jul 2011

Cite this

de Kreuk, B. J., Nethe, M., Fernandez-Borja, M., Anthony, E. C., Hensbergen, P. J., Deelder, A. M., ... Hordijk, P. L. (2011). The F-BAR domain protein PACSIN2 associates with Rac1 and regulates cell spreading and migration. Journal of Cell Science, 124(14), 2375-2388. https://doi.org/10.1242/jcs.080630