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.
|Titolo:||Direct interaction between exocyst and Wave complexes promotes cell protrusions and motility|
SCITA, GIORGIO [Investigation]
|Parole Chiave:||Exocyst; Motility; Ral; Wave; Adaptor Proteins, Signal Transducing; Cell Surface Extensions; Cytoskeletal Proteins; HEK293 Cells; Humans; Multiprotein Complexes; Protein Binding; Protein Subunits; Vesicular Transport Proteins; Wiskott-Aldrich Syndrome Protein Family; Cell Movement; Cell Biology|
|Settore Scientifico Disciplinare:||Settore MED/04 - Patologia Generale|
|Data di pubblicazione:||15-ott-2016|
|Digital Object Identifier (DOI):||10.1242/jcs.187336|
|Appare nelle tipologie:||01 - Articolo su periodico|