Arl1 gets into the membrane remodeling business with a flippase and ArfGEF

Abstract

Small GTP-binding proteins in the ADP ribosylation factor (Arf) family are master regulators of vesicle-mediated protein transport in the secretory and endocytic pathways (1). There are multiple members of this family in eukaryotic cells, with the lineage starting with Arf1 and its siblings (Arf2–Arf5) and extending to the more distant relatives Arf6, Sar1, and Arf-like (Arl) proteins. All these proteins cycle between GTP-bound and GDP-bound states with the assistance of guanine nucleotide exchange factors (GEFs) and GTPase activating proteins. The best known function of GTP-bound Arfs is to recruit vesicle coat proteins from the cytosol onto the appropriate membrane for the purpose of budding a transport vesicle. However, a few links between Arfs and lipid modifying events have been reported (1). In PNAS, Tsai et al. report a unique function for Arl1, arguably the least understood member of the Arf family, in stimulating the activity of a phospholipid flippase in the trans-Golgi network (TGN) of budding yeast (2). Remarkably, this function of Arl1 also requires interaction with an ArfGEF (not an ArlGEF), infusing a bit of intrigue into the Arf family tree. These interactions are shown to be important for protein transport from the Golgi and the establishment of membrane asymmetry (2) (Fig. 1).