A functional role for the GCC185 golgin in mannose 6-phosphate receptor recycling

Mol Biol Cell. 2006 Oct;17(10):4353-63. doi: 10.1091/mbc.e06-02-0153. Epub 2006 Aug 2.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins / metabolism
  • Endosomes / metabolism
  • Golgi Apparatus / metabolism*
  • Golgi Apparatus / ultrastructure
  • Golgi Matrix Proteins
  • HeLa Cells
  • Humans
  • Intracellular Signaling Peptides and Proteins*
  • Membrane Proteins / metabolism
  • Membrane Proteins / physiology*
  • Models, Biological
  • RNA, Small Interfering
  • Receptor, IGF Type 2 / metabolism*
  • Transfection
  • Transport Vesicles / metabolism
  • trans-Golgi Network / metabolism*
  • trans-Golgi Network / ultrastructure

Substances

  • Cell Cycle Proteins
  • GCC2 protein, human
  • Golgi Matrix Proteins
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • RNA, Small Interfering
  • Receptor, IGF Type 2
  • rad9 protein