Arf Regulates Interaction of GGA with Mannose-6-Phosphate Receptor

Authors

  • Dianne Snow Hirsch,

    1. Laboratory of Cellular Oncology, Center for Cancer Research, National Cancer Institute, Bldg 37 Room 6032 and
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    • The first two authors contributed equally to this work

  • Katherine T. Stanley,

    1. Laboratory of Cellular Oncology, Center for Cancer Research, National Cancer Institute, Bldg 37 Room 6032 and
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    • The first two authors contributed equally to this work

  • Ling-Xin Chen,

    1. Laboratory of Cellular Oncology, Center for Cancer Research, National Cancer Institute, Bldg 37 Room 6032 and
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  • Kerry M. Jacques,

    1. Laboratory of Cellular Oncology, Center for Cancer Research, National Cancer Institute, Bldg 37 Room 6032 and
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  • Rosa Puertollano,

    1. Cell Biology and Metabolism Branch, National Institute of Child Health and Development, National Institutes of Health, Bethesda. MD 20892, USA
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  • Paul A. Randazzo

    Corresponding author
    1. Laboratory of Cellular Oncology, Center for Cancer Research, National Cancer Institute, Bldg 37 Room 6032 and
      Corresponding author: Paul A. Randazzo
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Corresponding author: Paul A. Randazzorandazzo@helix.nih.gov

Abstract

The role of ADP-ribosylation factor (Arf) in Golgi associated, γ-adaptin homologous, Arf-interacting protein (GGA)-mediated membrane traffic was examined. GGA is a clathrin adaptor protein that binds Arf through its GAT domain and the mannose-6-phosphate receptor through its VHS domain. The GAT and VHS domains interacted such that Arf and mannose-6-phosphate receptor binding to GGA were mutually exclusive. In vivo, GGA bound membranes through either Arf or mannose-6-phosphate receptor. However, mannose-6-phosphate receptor excluded Arf from GGA-containing structures outside of the Golgi. These data are inconsistent with predictions based on the model for Arf's role in COPI veside coat function. We propose that Arf recruits GGA to a membrane and then, different from the current model, ‘hands-off’ GGA to mannose-6-phosphate receptor. GGA and mannose-6-phosphate receptor are then incorporated into a transport intermediate that excludes Arf.

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