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Jean S, Tremblay MG, Herdman C, et al. The endocytic adapter E-Syt2 recruits the p21 GTPase activated kinase PAK1 to mediate actin dynamics and FGF signalling. Biol Open. 2012;1(8):731-8doi: 10.1242/bio.2012968.
Jean, S., Tremblay, M. G., Herdman, C., Guillou, F., & Moss, T. (2012). The endocytic adapter E-Syt2 recruits the p21 GTPase activated kinase PAK1 to mediate actin dynamics and FGF signalling. Biology open, 1(8), 731-8. https://doi.org/10.1242/bio.2012968
Jean, Steve, et al. "The endocytic adapter E-Syt2 recruits the p21 GTPase activated kinase PAK1 to mediate actin dynamics and FGF signalling." Biology open vol. 1,8 (2012): 731-8. doi: https://doi.org/10.1242/bio.2012968
Jean S, Tremblay MG, Herdman C, Guillou F, Moss T. The endocytic adapter E-Syt2 recruits the p21 GTPase activated kinase PAK1 to mediate actin dynamics and FGF signalling. Biol Open. 2012 Aug 15;1(8):731-8. doi: 10.1242/bio.2012968. Epub 2012 Jun 12. PMID: 23213466; PMCID: PMC3507230.
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Biol Open. 2012 Aug 15;1(8):731-8. doi: 10.1242/bio.2012968. Epub 2012 Jun 12.

The endocytic adapter E-Syt2 recruits the p21 GTPase activated kinase PAK1 to mediate actin dynamics and FGF signalling.

Biology open

Steve Jean, Michel G Tremblay, Chelsea Herdman, François Guillou, Tom Moss

Affiliations

  1. Present address: Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093-0380, USA.

PMID: 23213466 PMCID: PMC3507230 DOI: 10.1242/bio.2012968

Abstract

Fibroblast growth factor (FGF) signalling plays an essential role in early vertebrate development. However, the response to FGF requires endocytosis of the activated FGF receptor (FGFR) that is in part dependent on remodelling of the actin cytoskeleton. Recently we showed that the extended synaptotagmin family plasma membrane protein, E-Syt2, is an essential endocytic adapter for FGFR1. Here we show E-Syt2 is also an interaction partner for the p21-GTPase Activated Kinase PAK1. The phospholipid binding C2C domain of E-Syt2 specifically binds a site adjacent to the CRIB/GBD of PAK1. PAK1 and E-Syt2 selectively complex with FGFR1 and functionally cooperate in the FGF signalling. E-Syt2 binding suppresses actin polymerization and inhibits the activation of PAK1 by the GTPases Cdc42 and Rac. Interestingly, the E-Syt2 binding site on PAK1 extensively overlaps a site recently suggested to bind phospholipids. Our data suggest that PAK1 interacts with phospholipid membrane domains via E-Syt2, where it may cooperate in the E-Syt2-dependent endocytosis of activated FGFR1 by modulating cortical actin stability.

Keywords: Cortical actin; E-Syt2; Endocytosis; Extended synaptotagmin; FGF receptor; FGF signalling; PAK1; p21-GTPase activated kinase

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