Coupling of membrane traffic and cytoskeleton remodeling in the regulation of cell motility

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Cell motility and cell division are under coordinated regulation of membrane traffic and actin cytoskeleton remodeling. The Arf and Rab families of small GTPases regulate membrane traffic, and the Rho family small GTPases regulate cytoskeleton remodeling. In this study, we showed that Arfaptins, which are dual effectors of Arl1 and Rac1, are recruited onto trans-Golgi membranes through interacting with Arl1, and induce membrane tubulation in an Arl1-dependent manner. X-ray crystal structure of the Arl1-Arfaptin-2 complex revealed the molecular basis for the membrane recruitment of Arfaptin-2 and indicated a possibility that Arl1 and Rac1 compete with each other for binding to Arfaptin-2.On the other hand, we showed that Arf6 is recruited to the Flemming body during cytokinesis through interacting with MLKP1, which forms a complex with MgcRacGAP, and is involved in regulation of cytokinesis. Furthermore, We revealed the structure of the Arf6-MKLP1 complex by X-ray crystallography and suggested the molecular basis for recruitment of Arf6 onto the Flemming body. We further showed that EFA6, an Arf-GEF, is involved in local activation of Arf6 during cytokinesis.