Journal
JOURNAL OF CELL SCIENCE
Volume 129, Issue 20, Pages 3756-3769Publisher
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/jcs.187336
Keywords
Wave; Exocyst; Motility; Ral
Categories
Funding
- Association pour la Recherche sur le Cancer [SFI20121205710, SFI20111203931]
- Ligue Contre le Cancer [RS14/75-54]
- Association Christelle Bouillot
- GenHomme Network [02490-6088]
- Associazione Italiana per la Ricerca sul Cancro [IG 14104]
- European Research Council [268836]
- Association for International Cancer Research [14-0335]
- Fondazione Cariplo
- Association pour la Recherche sur le Cancer, Ligue Contre le Cancer
- European Molecular Biology Organization
- Vinci program of the Universite' Franco-Italienne
- European Research Council (ERC) [268836] Funding Source: European Research Council (ERC)
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Coordination between membrane trafficking and actin polymerization is fundamental in cell migration, but a dynamic view of the underlying molecular mechanisms is still missing. The Rac1 GTPase controls actin polymerization at protrusions by interacting with its effector, the Wave regulatory complex (WRC). The exocyst complex, which functions in polarized exocytosis, has been involved in the regulation of cell motility. Here, we show a physical and functional connection between exocyst and WRC. Purified components of exocyst and WRC directly associate in vitro, and interactions interfaces are identified. The exocyst-WRC interaction is confirmed in cells by co-immunoprecipitation and is shown to occur independently of the Arp2/3 complex. Disruption of the exocyst-WRC interaction leads to impaired migration. By using time-lapse microscopy coupled to image correlation analysis, we visualized the trafficking of the WRC towards the front of the cell in nascent protrusions. The exocyst is necessary for WRC recruitment at the leading edge and for resulting cell edge movements. This direct link between the exocyst and WRC provides a new mechanistic insight into the spatio-temporal regulation of cell migration.
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