Diacylglycerol Kinase α Controls RCP-dependent Integrin Trafficking to Promote Invasive Migration

Overview

Journal J Cell Biol

Specialty Cell Biology

Date 2012 Jan 25

PMID 22270919

Citations 76

Authors

Elena Rainero

Patrick T Caswell

Patricia A J Muller

Joan Grindlay

Mary W McCaffrey

Qifeng Zhang

Michael J O Wakelam

Karen H Vousden

Andrea Graziani

Jim C Norman

Affiliations

Soon will be listed here.

Abstract

Inhibition of αvβ3 integrin or expression of oncogenic mutants of p53 promote invasive cell migration by enhancing endosomal recycling of α5β1 integrin under control of the Rab11 effector Rab-coupling protein (RCP). In this paper, we show that diacylglycerol kinase α (DGK-α), which phosphorylates diacylglycerol to phosphatidic acid (PA), was required for RCP to be mobilized to and tethered at the tips of invasive pseudopods and to allow RCP-dependent α5β1 recycling and the resulting invasiveness of tumor cells. Expression of a constitutive-active mutant of DGK-α drove RCP-dependent invasion in the absence of mutant p53 expression or αvβ3 inhibition, and conversely, an RCP mutant lacking the PA-binding C2 domain was not capable of being tethered at pseudopod tips. These data demonstrate that generation of PA downstream of DGK-α is essential to connect expression of mutant p53s or inhibition of αvβ3 to RCP and for this Rab11 effector to drive the trafficking of α5β1 that is required for tumor cell invasion through three-dimensional matrices.

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