Grp1-associated scaffold protein (GRASP) is a regulator of the ADP ribosylation factor 6 (Arf6)-dependent membrane trafficking pathway

Authors

  • Anand Venkataraman,

    1. Program in Molecular and Cellular Biology and the Department of Pharmaceutical Sciences, Oregon State University, Corvallis, OR 97331, U.S.A.
    Search for more papers by this author
    • Department of Pharmacology, University of Pennsylvania School of Medicine, 835 BRB 421 Curie Blvd, Philadelphia, PA 19104, U.S.A.

  • Daniel J. Nevrivy,

    1. Program in Molecular and Cellular Biology and the Department of Pharmaceutical Sciences, Oregon State University, Corvallis, OR 97331, U.S.A.
    Search for more papers by this author
    • Nevrivy Patent Law Group P.L.L.C., 1055 Thomas Jefferson Street, N.W Suite M-100, Washington DC 20007, U.S.A.

  • Theresa M. Filtz,

    1. Program in Molecular and Cellular Biology and the Department of Pharmaceutical Sciences, Oregon State University, Corvallis, OR 97331, U.S.A.
    Search for more papers by this author
  • Mark Leid

    Corresponding author
    1. Program in Molecular and Cellular Biology and the Department of Pharmaceutical Sciences, Oregon State University, Corvallis, OR 97331, U.S.A.
    Search for more papers by this author

(email Mark.Leid@oregonstate.edu)

Abstract

GRASP interacts with Grp1 (general receptor for phosphoinositides 1; cytohesin 3), which catalyses nucleotide exchange on and activation of Arf6 (ADP-ribosylation factor-6). Arf6 is a low-molecular-mass GTPase that regulates key aspects of endocytic recycling pathways. Overexpressed GRASP accumulated in the juxtanuclear ERC (endocytic recycling compartment). GRASP co-localized with a constitutively inactive mutant of Arf6 in the ERC such that it was reversed by expression of wild-type Grp1. Co-expression of GRASP and Grp1 promoted membrane ruffling, a cellular hallmark of Arf6 activation. GRASP accumulation in ERC was found to block recycling of the MHC-I (major histocompatibility complex-I), which is trafficked by the Arf6-dependent pathway. In contrast, overexpression of GRASP had no effect on the recycling of transferrin receptors, which are trafficked by a clathrin-dependent pathway. The findings suggest that GRASP regulates the non-clathrin/Arf6-dependent, plasma membrane recycling and signalling pathways.

Ancillary