Regulation of Microtubule-dependent Recycling at theTrans-Golgi Network by Rab6A and Rab6A'
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Published:2005-01
Issue:1
Volume:16
Page:162-177
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ISSN:1059-1524
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Container-title:Molecular Biology of the Cell
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language:en
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Short-container-title:MBoC
Author:
Young Joanne1, Stauber Tobias1, del Nery Elaine1, Vernos Isabelle1, Pepperkok Rainer1, Nilsson Tommy1
Affiliation:
1. Cell Biology and Biophysics Programme, European Molecular Biology Laboratory, D-69117 Heidelberg, Germany
Abstract
The small GTPase rab6A but not the isoform rab6A' has previously been identified as a regulator of the COPI-independent recycling route that carries Golgi-resident proteins and certain toxins from the Golgi to the endoplasmic reticulum (ER). The isoform rab6A' has been implicated in Golgi-to-endosomal recycling. Because rab6A but not A', binds rabkinesin6, this motor protein is proposed to mediate COPI-independent recycling. We show here that both rab6A and rab6A' GTP-restricted mutants promote, with similar efficiency, a microtubule-dependent recycling of Golgi resident glycosylation enzymes upon overexpression. Moreover, we used small interfering RNA mediated down-regulation of rab6A and A' expression and found that reduced levels of rab6 perturbs organization of the Golgi apparatus and delays Golgi-to-ER recycling. Rab6-directed Golgi-to-ER recycling seems to require functional dynactin, as overexpression of p50/dynamitin, or a C-terminal fragment of Bicaudal-D, both known to interact with dynactin inhibit recycling. We further present evidence that rab6-mediated recycling seems to be initiated from the trans-Golgi network. Together, this suggests that a recycling pathway operates at the level of the trans-Golgi linking directly to the ER. This pathway would be the preferred route for both toxins and resident Golgi proteins.
Publisher
American Society for Cell Biology (ASCB)
Subject
Cell Biology,Molecular Biology
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