Clathrin is required for Scar/Wave-mediated lamellipodium formation.
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.
CNRS UPR3082, Laboratoire d'Enzymologie et Biochimie Structurales, Avenue de la Terrasse, 91198 Gif-sur-Yvette Cedex,  France.
Jérémie J
JJ
Gautier
Maria E
ME
Lomakina
Lamia
L
Bouslama-Oueghlani
Emmanuel
E
Derivery
Helen
H
Beilinson
Wolfgang
W
Faigle
Damarys
D
Loew
Daniel
D
Louvard
Arnaud
A
Echard
Antonina Y
AY
Alexandrova
Buzz
B
Baum
Alexis
A
Gautreau
D000818:Animals; D002465:Cell Movement / Q000235:genetics; D022081:Cell Surface Extensions / Q000378:metabolism / Q000473:pathology; D002966:Clathrin / Q000235:genetics / Q000378:metabolism*; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding / Q000235:genetics; D021381:Protein Transport / Q000235:genetics; D040901:Proteomics; D011554:Pseudopodia / Q000378:metabolism* / Q000473:pathology; D017384:Sequence Deletion / Q000235:genetics; D019076:Transgenes / Q000235:genetics; D051300:Wiskott-Aldrich Syndrome Protein Family / Q000235:genetics / Q000378:metabolism
D002966:Clathrin; D029721:Drosophila Proteins; D008840:Microfilament Proteins; C449671:SCAR protein, Drosophila; C114864:WASF1 protein, human; D051300:Wiskott-Aldrich Syndrome Protein Family