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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.
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    • 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.
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    • 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.
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  • 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.
      (email Mark.Leid@oregonstate.edu)
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(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.

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