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PMID: 12773381 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

The EMBO journal ·Vol. 22 ·No. 11 ·2003-06-02 ·Pages 2645-57

Deneka M, Neeft M, Popa I, van Oort M, Sprong H, Oorschot V, Klumperman J, Schu P, van der Sluijs P

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.

MeSH Terms
Adaptor Protein Complex gamma Subunits/chemistry,metabolism Animals Carrier Proteins/chemistry,genetics,metabolism Cell Membrane/metabolism Endosomes/metabolism HeLa Cells Humans Macromolecular Substances Membrane Proteins/chemistry,metabolism Mice Protein Binding RNA Interference Recombinant Fusion Proteins/chemistry,genetics,metabolism Transcription Factor AP-1/chemistry,metabolism Vesicular Transport Proteins rab4 GTP-Binding Proteins/chemistry,genetics,metabolism
Chemicals
Adaptor Protein Complex gamma Subunits Carrier Proteins Macromolecular Substances Membrane Proteins RABEP1 protein, human Rabep1 protein, mouse Recombinant Fusion Proteins Transcription Factor AP-1 Vesicular Transport Proteins rab4 GTP-Binding Proteins
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Deneka Magdalena
Department of Cell Biology and Institute of Biomembranes, University Medical Center, NL-3584 CX Utrecht, The Netherlands.
Neeft Maaike
Popa Ioana
van Oort Masja
Sprong Hein
Oorschot Viola
Klumperman Judith
Schu Peter
van der Sluijs Peter
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
2003-06-02
Pages
2645-57
Language
English
Region
England
NLM ID
8208664
PMCID
PMC156754
Subset
IM
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