Bicaudal-D regulates COPI-independent Golgi-ER transport by recruiting the dynein-dynactin motor complex.
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.
Matanis
Theodoros
T
Department of Experimental Tumorbiology, University of Muenster, Badestrasse 9, D-48149 Muenster, Germany.
Akhmanova
Anna
A
Wulf
Phebe
P
Del Nery
Elaine
E
Weide
Thomas
T
Stepanova
Tatiana
T
Galjart
Niels
N
Grosveld
Frank
F
Goud
Bruno
B
De Zeeuw
Chris I
CI
Barnekow
Angelika
A
Hoogenraad
Casper C
CC
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
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