Heterotrimeric G proteins interact with the small GTPase ARF. Possibilities for the regulation of vesicular traffic

COLOMBO MI; INGLESE J; D'SOUZA-SCHOREY C; BERON W; STAHL PD

JOURNAL OF BIOLOGICAL CHEMISTRY

AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC

Lugar: Bethesda, Maryland; Año: 1995 vol. 270 p. 24564 - 24571

0021-9258

Trimeric G proteins have emerged as important regulators of membrane trafficking. To explore a role for Gβγ in endosome fusion, we have taken advantage of β-adrenergic receptor kinase (βARK), an enzyme translocated to membranes by interaction with Gβγ. The COOH terminus of βARK (βARKct) has a Gβγ-binding domain which blocks some Gβγ-mediated processes. We found that βARKct and peptide G, a peptide derived from βARKct, inhibit in vitro endosome fusion. Interestingly, peptide G and ARF share sequence similarity. Peptide G and βARKct reversed ARF-mediated inhibition of endosome fusion and blocked ARF binding to membranes. Using an ARF fusion protein, we show that both Gβγ and Gαs interact with the small GTPase ARF, an interaction that is regulated by nucleotide binding. We conclude that G proteins may participate in the regulation of vesicular trafficking by directly interacting with ARF, a cytosolic factor required for transport.