Rabaptin-5 alpha/rabaptin-4 serves as a linker between rab4 and gamma(1)-adaptin in membrane recycling from endosomes

M Deneka, M Neeft, [No Value] Popa, M van Oort, H Sprong, [No Value] Oorschot, J Klumperman, P Schu, P van der Sluijs*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

72 Citations (Scopus)

Abstract

Rab4 regulates recycling from early endosomes. We investigated the role of the rab4 effector rabaptin-5alpha and its putative partner gamma(1)-adaptin in membrane recycling. We found that rabaptin-5alpha forms a ternary complex with the gamma(1)-sigma(1) subcomplex of AP-1, via a direct interaction with the gamma(1)-subunit. The binding site for gamma(1)-adaptin is in the hinge region of rabaptin-5alpha, which is distinct from rab4- and rab5-binding domains. Endogenous or ectopically expressed gamma(1)- adaptin localized to both the trans-Golgi network and endosomes. Co-expressed rabaptin-5alpha and gamma(1)-adaptin, however, co-localized in a rab4-dependent manner on recycling endosomes. Transfection of rabaptin-5alpha caused enlarged endosomes and delayed recycling of transferrin. RNAi of rab4 had an opposing effect on transferrin recycling. Collectively, our data show that rab4-GTP acts as a scaffold for a rabaptin-5alpha- gamma(1)-adaptin complex on recycling endosomes and that interactions between rab4, rabaptin-5alpha and gamma(1)-adaptin regulate membrane recycling.

Original languageEnglish
Pages (from-to)2645-2657
Number of pages13
JournalEMBO Journal
Volume22
Issue number11
Publication statusPublished - 2-Jun-2003

Keywords

  • gamma 1-adaptin
  • endosomes
  • rab4
  • rabaptin-5 alpha
  • receptor recycling
  • SMALL GTPASE RAB5
  • GAMMA-ADAPTIN
  • ENDOCYTIC PATHWAY
  • BINDING PROTEIN
  • VESICLES
  • CLATHRIN
  • DOMAIN
  • CELLS
  • COMPLEXES
  • EFFECTOR

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