QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online 19 December 2006
doi: 10.1242/jcs.03333

This Article Figures Only Full Text Full Text (PDF) Supplementary Material All Versions of this Article: jcs.03333v1 120/2/289    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JCS Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Evans, I. R. Articles by Nobes, C. D. Search for Related Content PubMed PubMed Citation Articles by Evans, I. R. Articles by Nobes, C. D. Social Bookmarking                         What's this?

Ena/VASP proteins mediate repulsion from ephrin ligands

¹ Department of Biochemistry, School of Medical Sciences, University of Bristol, University Walk, Bristol, BS8 1TD, UK
² Institute for Clinical Biochemistry and Pathobiochemistry, University of Würtzburg, Würtzburg, Germany
³ Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA
⁴ Department of Physiology, School of Medical Sciences, University of Bristol, University Walk, Bristol, BS8 1TD, UK

^* Author for correspondence (e-mail: catherine.nobes{at}bristol.ac.uk)

Accepted 9 November 2006

Ena/VASP proteins negatively regulate cell motility and contribute to repulsion from several guidance cues; however, there is currently no evidence for a role downstream of Eph receptors. Eph receptors mediate repulsion from ephrins at sites of intercellular contact during several developmental migrations. For example, the expression of ephrin-Bs in posterior halves of somites restricts neural crest cell migration to the anterior halves. Here we show that ephrin-B2 destabilises neural crest cell lamellipodia when presented in a substrate-bound or soluble form. Our timelapse studies show that repulsive events are associated with the rearward collapse and subsequent loss of lamellipodia as membrane ruffles. We hypothesise that Ena/VASP proteins contribute to repulsion from ephrins by destabilising cellular protrusions and show that Ena/VASP-deficient fibroblasts exhibit reduced repulsion from both ephrin-A and ephrin-B stripes compared to wild-type controls. Moreover, when EphB4 and ephrin-B2 were expressed in neighbouring Swiss 3T3 fibroblasts, VASP and Mena co-accumulated with activated Eph receptors at protrusions formed by EphB4-expressing cells. Sequestration of Ena/VASP proteins away from the periphery of these cells inhibited Eph receptor internalisation, a process that facilitates repulsion. Our results suggest that Ena/VASP proteins regulate ephrin-induced Eph receptor signalling events, possibly by destabilising lamellipodial protrusions.

Key words: Ena/VASP, Eph, Ephrin, Repulsion, Neural crest

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

Related articles in JCS:

Eph-ective cell repulsion

JCS 2007 120: 204. [Full Text]  

This article has been cited by other articles:

				T. M. Coate, J. A. Wirz, and P. F. Copenhaver Reverse Signaling via a Glycosyl-Phosphatidylinositol-Linked Ephrin Prevents Midline Crossing by Migratory Neurons during Embryonic Development in Manduca J. Neurosci., April 9, 2008; 28(15): 3846 - 3860. [Abstract] [Full Text] [PDF]

				L. Trichet, C. Sykes, and J. Plastino Relaxing the actin cytoskeleton for adhesion and movement with Ena/VASP J. Cell Biol., April 3, 2008; 181(1): 19 - 25. [Abstract] [Full Text] [PDF]