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  • The EMBO Journal (2003) 22, 78 - 88
  • doi:10.1093/emboj/cdg015

Divalent interaction of the GGAs with the Rabaptin-5–Rabex-5 complex

Rafael Mattera1, Cecilia N. Arighi1, Robert Lodge1, Marino Zerial2 and Juan S. Bonifacino1

  1. Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
  2. Max Planck Institute for Molecular Cell Biology and Genetics, Pfotenhauerstrasse, D-01307 Dresden, Germany

Correspondence to:

Juan S. Bonifacino, E-mail: juan@helix.nih.gov

Received 11 July 2002; Accepted 11 November 2002; Revised 1 November 2002

Cargo transfer from trans-Golgi network (TGN)-derived transport carriers to endosomes involves a still undefined set of tethering/fusion events. Here we analyze a molecular interaction that may play a role in this process. We demonstrate that the GGAs, a family of Arf-dependent clathrin adaptors involved in selection of TGN cargo, interact with the Rabaptin-5–Rabex-5 complex, a Rab4/Rab5 effector regulating endosome fusion. These interactions are bipartite: GGA-GAE domains recognize an FGPLV sequence (residues 439–443) in a predicted random coil of Rabaptin-5 (a sequence also recognized by the gamma1- and gamma2-adaptin ears), while GGA-GAT domains bind to the C-terminal coiled-coils of Rabaptin-5. The GGA–Rabaptin-5 interaction decreases binding of clathrin to the GGA-hinge domain, and expression of green fluorescent protein (GFP)–Rabaptin-5 shifts the localization of endogenous GGA1 and associated cargo to enlarged early endosomes. These observations thus identify a binding sequence for GAE/gamma-adaptin ear domains and reveal a functional link between proteins regulating TGN cargo export and endosomal tethering/fusion events.

  • Keywords:

    • clathrin,
    • endosomes,
    • GGA,
    • Rabaptin-5,
    • Rabex-5