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Differential Rac1 signalling by guanine nucleotide exchange factors implicates FLII in regulating Rac1-driven cell migration

Abstract

The small GTPase Rac1 has been implicated in the formation and dissemination of tumours. Upon activation by guanine nucleotide exchange factors (GEFs), Rac1 associates with a variety of proteins in the cell thereby regulating various functions, including cell migration. However, activation of Rac1 can lead to opposing migratory phenotypes raising the possibility of exacerbating tumour progression when targeting Rac1 in a clinical setting. This calls for the identification of factors that influence Rac1-driven cell motility. Here we show that Tiam1 and P-Rex1, two Rac GEFs, promote Rac1 anti- and pro-migratory signalling cascades, respectively, through regulating the Rac1 interactome. In particular, we demonstrate that P-Rex1 stimulates migration through enhancing the interaction between Rac1 and the actin-remodelling protein flightless-1 homologue, to modulate cell contraction in a RhoA-ROCK-independent manner.

Type Journal
ISBN 2041-1723 (Electronic) 2041-1723 (Linking)
Authors Marei, H.; Carpy, A.; Woroniuk, A.; Vennin, C.; White, G.; Timpson, P.; Macek, B.; Malliri, A.;
Publisher Name Nature Communications
Published Date 2016-02-01 00:00:00
Published Volume 7
Published Pages 10664
URL http://www.ncbi.nlm.nih.gov/pubmed/26887924
Status Published In-print
OpenAccess Link https://publications.gimr.garvan.org.au/download.php?13667_13630/2016-Marei-Nat Commun.pdf