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ADP-ribosylation factors (ARFs) play important roles in both constitutive and regulated membrane trafficking to the plasma membrane in other cells. Here we have examined their role in insulin-stimulated GLUT4 translocation in 3T3-L1 adipocytes. These cells express ARF5 and ARF6. ARF5 was identified in the soluble protein and intracellular membranes; in response to insulin some ARF5 was observed to re-locate to the plasma membrane. In contrast, ARF6 was predominantly localized to the plasma membrane and did not redistribute in response to insulin. We employed myristoylated peptides corresponding to the NH2 termini of ARF5 and ARF6 to investigate the function of these proteins. Myr-ARF6 peptide inhibited insulin-stimulated glucose transport and GLUT4 translocation by approximately 50% in permeabilized adipocytes. In contrast, myr-ARF1 and myr-ARF5 peptides were without effect. Myr-ARF5 peptide also inhibited the insulin stimulated increase in cell surface levels of GLUT1 and transferrin receptors. Myr-ARF6 peptide significantly decreased cell surface levels of these proteins in both basal and insulin-stimulated states, but did not inhibit the fold increase in response to insulin. These data suggest an important role for ARF6 in regulating cell surface levels of GLUT4 in adipocytes, and argue for a role for both ARF5 and ARF6 in the regulation of membrane trafficking to the plasma membrane.

Original publication

DOI

10.1074/jbc.274.25.17619

Type

Journal article

Journal

J Biol Chem

Publication Date

18/06/1999

Volume

274

Pages

17619 - 17625

Keywords

3T3 Cells, ADP-Ribosylation Factor 1, ADP-Ribosylation Factors, Amino Acid Sequence, Animals, Biological Transport, Deoxyglucose, GTP-Binding Proteins, Glucose Transporter Type 1, Glucose Transporter Type 4, Insulin, Membrane Proteins, Mice, Molecular Sequence Data, Monosaccharide Transport Proteins, Muscle Proteins, Myristic Acids, Peptide Fragments, Receptors, Transferrin