HETEROTRIMERIC G-PROTEINS INTERACT WITH THE SMALL GTPASE ARF - POSSIBILITIES FOR THE REGULATION OF VESICULAR TRAFFIC

Trimeric G proteins have emerged as important regulators of membrane t rafficking. To explore a role for G beta gamma in endosome fusion, we have taken advantage of beta-adrenergic receptor kinase (beta ARK), an enzyme translocated to membranes by interaction with G beta gamma, Th e COOH terminus of beta ARK (beta ARKct) has a G beta gamma-binding do main which blocks some G beta gamma-mediated processes. We found that beta ARKct and peptide G, a peptide derived from beta ARKct, inhibit i n vitro endosome fusion. Interestingly, peptide G and ARF share sequen ce similarity. Peptide G and beta ARKct reversed ARF-mediated inhibiti on of endosome fusion and blocked ARF binding to membranes. Using an A RF fusion protein, we show that both G beta gamma and G alpha s intera ct with the small GTPase ARF, an interaction that is regulated by nucl eotide binding. We conclude that G proteins may participate in the reg ulation of vesicular trafficking by directly interacting with ARF, a c ytosolic factor required for transport.