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Relationship between plasma membrane trafficking and actin dynamics

Role of PIP2 and PIP5-kinase in mediating changes in trafficking and actin

Regulators of Arf6 activation

The ADP-ribosylation factors (ARFs) are a family of GTP binding proteins that regulate membrane traffic and organelle structure in the cell . We are studying the function of ARF6, which affects plasma membrane (PM) traffic and the actin cytoskeleton. We have demonstrated that ARF6 regulates the movement of PM into and out of a novel, endosomal recycling pathway that influences cell surface morphology. The return of membrane and ARF6 to the PM occurs at discrete sites along the peripheral edges of cells and is associated with cortical actin polymerization and the formation of protrusions. We have demonstrated that this ARF6-regulated, membrane recycling pathway is required during cell spreading and for the actin rearrangements and membrane ruffling observed with activated forms of Rac1 GTPase. By contrast, ARF6-induced actin rearrangements occur independently of any Rho proteins. The requirement for ARF6 activity for cell spreading, and Rac-induced ruffling implicates the ARF6-regulated membrane recycling pathway as being a critical component for cell shape alterations that may occur during the cell cycle, cell migration, differentiation, and metastasis. We are currently investigating potential regulators of ARF6 activation and downstream targets which mediate ARF6 function.