ARF6 plays a general role in targeting palmitoylated proteins from golgi to the plasma membrane.

Abstract

Protein palmitoylation is a post-translational lipid modification of proteins. Accumulating evidences reveal that palmitoylation functions as a sorting signal to direct proteins to destinations; however, the sorting mechanism remains largely unknown. Here, we show that ARF6 plays a general role in targeting palmitoylated proteins from Golgi to the plasma membrane (PM). Through a shRNA screening, we identify ARF6 as the key small GTPase in targeting CD36, a palmitoylated protein, from Golgi to PM. The N-terminal myristoylation of ARF6 is required for its binding with palmitoylated CD36, and the GTP-bound form of ARF6 facilitates the delivery of CD36 to the PM. Analysis of stable isotope labeling by amino acids reveals that ARF6 might facilitate the sorting of 359 of the 531 palmitoylated PM proteins, indicating a general role of ARF6. Our studies have thus identified a sorting mechanism for targeting palmitoylated proteins from Golgi to the PM.