title: Bicaudal-D regulates COPI-independent Golgi-ER transport by recruiting the dynein-dynactin motor complex.
abstract: The small GTPase Rab6a is involved in the regulation of membrane traffic from the Golgi apparatus towards the endoplasmic reticulum (ER) in a coat complex coatomer protein I (COPI)-independent pathway. Here, we used a yeast two-hybrid approach to identify binding partners of Rab6a. In particular, we identified the dynein-dynactin-binding protein Bicaudal-D1 (BICD1), one of the two mammalian homologues of Drosophila Bicaudal-D. BICD1 and BICD2 colocalize with Rab6a on the trans-Golgi network (TGN) and on cytoplasmic vesicles, and associate with Golgi membranes in a Rab6-dependent manner. Overexpression of BICD1 enhances the recruitment of dynein-dynactin to Rab6a-containing vesicles. Conversely, overexpression of the carboxy-terminal domain of BICD, which can interact with Rab6a but not with cytoplasmic dynein, inhibits microtubule minus-end-directed movement of green fluorescent protein (GFP)-Rab6a vesicles and induces an accumulation of Rab6a and COPI-independent ER cargo in peripheral structures. These data suggest that coordinated action between Rab6a, BICD and the dynein-dynactin complex controls COPI-independent Golgi-ER transport.
authors.affiliation: Department of Experimental Tumorbiology, University of Muenster, Badestrasse 9, D-48149 Muenster, Germany.
authors.forename: Theodoros
authors.initials: T
authors.lastname: Matanis
authors.forename: Anna
authors.initials: A
authors.lastname: Akhmanova
authors.forename: Phebe
authors.initials: P
authors.lastname: Wulf
authors.forename: Elaine
authors.initials: E
authors.lastname: Del Nery
authors.forename: Thomas
authors.initials: T
authors.lastname: Weide
authors.forename: Tatiana
authors.initials: T
authors.lastname: Stepanova
authors.forename: Niels
authors.initials: N
authors.lastname: Galjart
authors.forename: Frank
authors.initials: F
authors.lastname: Grosveld
authors.forename: Bruno
authors.initials: B
authors.lastname: Goud
authors.forename: Chris I
authors.initials: CI
authors.lastname: De Zeeuw
authors.forename: Angelika
authors.initials: A
authors.lastname: Barnekow
authors.forename: Casper C
authors.initials: CC
authors.lastname: Hoogenraad
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000502:physiology; D019556:COS Cells; D020755:Coat Protein Complex I / Q000502:physiology; D020756:Coatomer Protein / Q000502:physiology*; D029721:Drosophila Proteins / Q000502:physiology*; D000072159:Dynactin Complex; D004398:Dyneins / Q000502:physiology*; D004721:Endoplasmic Reticulum / Q000502:physiology*; D006056:Golgi Apparatus / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000502:physiology*; D020409:Molecular Motor Proteins / Q000502:physiology; D008969:Molecular Sequence Data; D020691:rab GTP-Binding Proteins / Q000502:physiology
chemical_list: C061998:BicD protein, Drosophila; D020755:Coat Protein Complex I; D020756:Coatomer Protein; D029721:Drosophila Proteins; D000072159:Dynactin Complex; D008869:Microtubule-Associated Proteins; D020409:Molecular Motor Proteins; C094135:Rab6 protein; D004398:Dyneins; D020691:rab GTP-Binding Proteins