Summary
The Scar/Wave complex (SWC) generates lamellipodia through Arp2/3-dependent polymerisation of branched actin networks. In order to identify new SWC regulators, we conducted a screen in Drosophila cells combining proteomics with functional genomics. This screen identified Clathrin heavy chain (CHC) as a protein that binds to the SWC and whose depletion affects lamellipodium formation. This role of CHC in lamellipodium formation can be uncoupled from its role in membrane trafficking by several experimental approaches. Furthermore, CHC is detected in lamellipodia in the absence of the adaptor and accessory proteins of endocytosis. We found that CHC overexpression decreased membrane recruitment of the SWC, resulting in reduced velocity of protrusions and reduced cell migration. By contrast, when CHC was targeted to the membrane by fusion to a myristoylation sequence, we observed an increase in membrane recruitment of the SWC, protrusion velocity and cell migration. Together these data suggest that, in addition to its classical role in membrane trafficking, CHC brings the SWC to the plasma membrane, thereby controlling lamellipodium formation.
Footnotes
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Funding
This work was supported by fellowships from the Ministère de l'Education et de la Recherche (to J.J.G. and E.D.); Ligue Nationale contre le Cancer (to L.B.O.); Agence Nationale pour la Recherche [grant number ANR-07-JCJC-0089-01 to A.E.]; University College of London (to B.B.); the Royal Society (to B.B.) and the Ludwig Institute for Cancer Research (to B.B.); the Russian Foundation for Basic Research [grant number 08-04-00452-a to A.Y.A.]. A.G. is supported by Fondation pour la Recherche Médicale; Association pour la Recherche sur le Cancer; and Agence Nationale pour la Recherche [grant numbers ANR-08-BLAN-0012-03, ANR-08-PCVI-0010-03].
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Supplementary material available online at http://jcs.biologists.org/lookup/suppl/doi:10.1242/jcs.081083/-/DC1
- Accepted June 20, 2011.
- © 2011.
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