Regulation of endosomal membrane traffic by a Gadkin/AP-1/kinesin KIF5 complex

Michael R. Schmidt, Tanja Maritzen, Viktoria Kukhtina, Victoria A. Higman, Laura Doglio, Naomi N. Barak, Holger Strauss, Hartmut Oschkinat, Carlos G. Dotti, Volker Haucke*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

64 Citations (Scopus)

Abstract

Endosomes and endosomal vesicles (EVs) rapidly move along cytoskeletal filaments allowing them to exchange proteins and lipids between different endosomal compartments, lysosomes, the trans-Golgi network (TGN), and the plasma membrane. The precise mechanisms that connect membrane traffic between the TGN and perinuclear endosomal compartments with motor-protein driven transport have largely remained elusive. Here we show that Gadkin (also termed gamma-BAR), a peripheral membrane protein localized to the TGN and to TGN-derived EVs, directly associates with the clathrin adaptor AP-1 and with the motor protein kinesin KIF5, thereby potentially regulating EV dynamics. Gadkin overexpression induced the dispersion of transferrin (Tf)- and Rab4-positive EVs to the cell periphery, whereas KIF5B-depleted cells displayed a perinuclear concentration. Functional experiments suggest that the role of Gadkin as a regulator of endosomal membrane traffic critically depends on complex formation with both AP-1 and KIF5. Our data thus provide a direct molecular link between TGN-derived EVs and the microtubule-based cytoskeleton.

Original languageEnglish
Pages (from-to)15344-15349
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number36
DOIs
Publication statusPublished - 8 Sep 2009

Keywords

  • clathrin adaptor AP-1
  • motor-protein driven transport
  • PLASMA-MEMBRANE
  • recycling
  • RECEPTOR
  • KINESIN
  • endosomal vesicles
  • RECYCLING ENDOSOMES
  • E-CADHERIN
  • RAB11

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