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Clathrin is required for Scar/Wave-mediated lamellipodium formation.
- Source :
-
Journal of cell science [J Cell Sci] 2011 Oct 15; Vol. 124 (Pt 20), pp. 3414-27. - Publication Year :
- 2011
-
Abstract
- 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.
- Subjects :
- Animals
Cell Movement genetics
Cell Surface Extensions metabolism
Cell Surface Extensions pathology
Clathrin genetics
Drosophila
Drosophila Proteins genetics
HeLa Cells
Humans
Microfilament Proteins genetics
Protein Binding genetics
Protein Transport genetics
Proteomics
Pseudopodia pathology
Sequence Deletion genetics
Transgenes genetics
Wiskott-Aldrich Syndrome Protein Family genetics
Wiskott-Aldrich Syndrome Protein Family metabolism
Clathrin metabolism
Drosophila Proteins metabolism
Microfilament Proteins metabolism
Pseudopodia metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1477-9137
- Volume :
- 124
- Issue :
- Pt 20
- Database :
- MEDLINE
- Journal :
- Journal of cell science
- Publication Type :
- Academic Journal
- Accession number :
- 22010197
- Full Text :
- https://doi.org/10.1242/jcs.081083