Roles of ARF6 and EFA6A in the development and maintenance of dendritic spines

Abstract

The cellular and molecular mechanisms underlying the development and maintenance of dendritic spines are not fully understood. ARF6 is a small GTPase known to regulate actin remodeling and membrane traffic. I studied involvement of ARF6 and EFA6A, an ARF6-specific exchange factor, in the regulation of spine development and maintenance. An active form of ARF6 promotes the formation of dendritic spines at the expense of filopodia. EFA6A promotes spine formation in an ARF6 activation-dependent manner. Knockdown of ARF6 and EFA6A by siRNA decreases spine formation. Live imaging indicates that ARF6 knockdown decreases the conversion of filopodia to spines and the stability of early spines. The spine promoting effect of ARF6 is partially blocked by Rae 1. ARF6 and EFA6A protect mature spines from inactivity-induced destabilization. These results suggest that ARF6 and EFA6A may regulate the conversion of filopodia to spines and the stability of both early and mature spines.