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© The Rockefeller University Press, 0021-9525/1999//743 $5.00
The Journal of Cell Biology, Volume 147, Number 4, , 1999 743-760

Rab6 Coordinates a Novel Golgi to ER Retrograde Transport Pathway in Live Cells

^a Light Microscopy Group, European Molecular Biology Laboratory, Meyerhofstrasse 1, D-69117 Heidelberg, Germany
^b Cell Biophysics and Cell Biology Programme, European Molecular Biology Laboratory, Meyerhofstrasse 1, D-69117 Heidelberg, Germany
^c Laboratoire Mécanismes moléculaires du transport intracellulaire, Institut Curie, CNRS UMR 144, Paris, Cedex 05, France
^d GBF-National Research Institute for Biotechnology, Department of Microbiology, Mascheroder Weg 1, 38124 Braunschweig, Germany
Light Microscopy Group and Cell Biophysics and Cell Biology Programme, European Molecular Biology Laboratory, Meyerhofstrasse 1, D-69117 Heidelberg, Germany.49 6221 387 30649 6221 387 123

jwhite{at}embl-heidelberg.de

We visualized a fluorescent-protein (FP) fusion to Rab6, a Golgi-associated GTPase, in conjunction with fluorescent secretory pathway markers. FP-Rab6 defined highly dynamic transport carriers (TCs) translocating from the Golgi to the cell periphery. FP-Rab6 TCs specifically accumulated a retrograde cargo, the wild-type Shiga toxin B-fragment (STB), during STB transport from the Golgi to the endoplasmic reticulum (ER). FP-Rab6 TCs associated intimately with the ER, and STB entered the ER via specialized peripheral regions that accumulated FP-Rab6. Microinjection of antibodies that block coatomer protein I (COPI) function inhibited trafficking of a KDEL-receptor FP-fusion, but not FP-Rab6. Additionally, markers of COPI-dependent recycling were excluded from FP-Rab6/STB TCs. Overexpression of Rab6:GDP (T27N mutant) using T7 vaccinia inhibited toxicity of Shiga holotoxin, but did not alter STB transport to the Golgi or Golgi morphology. Taken together, our results indicate Rab6 regulates a novel Golgi to ER transport pathway.

Key Words: intracellular transport • Shiga toxin • Rab6 protein • KDEL receptor • green fluorescent protein

© 1999 The Rockefeller University Press

Drs. Goud and Stelzer are principal investigators.

Drs. White and Johannes contributed equally.

Dr. Reinsch's present address is Gravitational Research Branch, NASA Ames Research Center, M/S 239-11, Moffett Field, CA 94035-1000.

. Abbreviations used in this paper: CFP, cyan fluorescent protein; CLSM, confocal laser scanning microscopy; COP, coatomer protein; CT, Cholera toxin; ER, endoplasmic reticulum; GFP, green fluorescent protein; KDELR, KDEL-receptor; PE, Pseudomonas exotoxin A; ST, Shiga toxin; STB, Shiga toxin B-fragment; TCs, transport carriers; YFP, yellow fluorescent protein.

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