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Vol. 17, Issue 10, 4353-4363, October 2006

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A Functional Role for the GCC185 Golgin in Mannose 6-Phosphate Receptor Recycling

Department of Biochemistry, Stanford University School of Medicine, Stanford, CA 94305-5307

Submitted February 22, 2006; Revised July 21, 2006; Accepted July 24, 2006
Monitoring Editor: Adam Linstedt

Mannose 6-phosphate receptors (MPRs) deliver newly synthesized lysosomal enzymes to endosomes and then recycle to the Golgi. MPR recycling requires Rab9 GTPase; Rab9 recruits the cytosolic adaptor TIP47 and enhances its ability to bind to MPR cytoplasmic domains during transport vesicle formation. Rab9-bearing vesicles then fuse with the trans-Golgi network (TGN) in living cells, but nothing is known about how these vesicles identify and dock with their target. We show here that GCC185, a member of the Golgin family of putative tethering proteins, is a Rab9 effector that is required for MPR recycling from endosomes to the TGN in living cells, and in vitro. GCC185 does not rely on Rab9 for its TGN localization; depletion of GCC185 slightly alters the Golgi ribbon but does not interfere with Golgi function. Loss of GCC185 triggers enhanced degradation of mannose 6-phosphate receptors and enhanced secretion of hexosaminidase. These data assign a specific pathway to an interesting, TGN-localized protein and suggest that GCC185 may participate in the docking of late endosome-derived, Rab9-bearing transport vesicles at the TGN.

This article was published online ahead of print in MBC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E06-02-0153) on August 2, 2006.

Address correspondence to: Suzanne R. Pfeffer (pfeffer{at}stanford.edu)

Abbreviations used: CD-MPR, cation-dependent mannose 6-phosphate receptor; CI-MPR, cation-independent mannose 6-phosphate receptor; MPR, mannose 6-phosphate receptor; siRNA, small interfering RNA; TIP47, tail-interacting protein of 47 kDa; VSVG, G protein of the vesicular stomatitis virus.

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