TBC1D23 is a bridging factor for endosomal vesicle capture by golgins at the trans-Golgi

Nat Cell Biol. 2017 Dec;19(12):1424-1432. doi: 10.1038/ncb3627. Epub 2017 Oct 30.

Abstract

The specificity of membrane traffic involves tethers at destination organelles that selectively capture incoming transport vesicles to allow SNAREs on opposing membranes to then assemble and drive fusion. Tethers include both protein complexes and long coiled-coil proteins, although how they contribute to specificity remains unclear. The golgin coiled-coil proteins at the Golgi apparatus capture vesicles from different origins, but the vesicle-specific molecular cues that they recognize are unknown. Vesicle tethering is typically a transient process and therefore is challenging to interrogate in vivo. Thus, we have used a system in which an ectopic golgin causes vesicles to accumulate in a tethered state. By applying proximity biotinylation to the golgin-captured vesicles, we identify TBC1D23, an apparently catalytically inactive member of a family of Rab GTPase-activating proteins (GAPs), as a vesicle-golgin adaptor that is required for endosome-to-Golgi trafficking. The Rab GAP domain of TBC1D23 binds to a conserved motif at the tip of golgin-245 and golgin-97 at the trans-Golgi, while the C terminus binds to the WASH complex on endosome-derived vesicles. Thus, TBC1D23 is a specificity determinant that links the vesicle to the target membrane during endosome-to-Golgi trafficking.

MeSH terms

  • Amino Acid Sequence
  • Autoantigens / chemistry
  • Autoantigens / metabolism
  • Endosomes / metabolism*
  • GTPase-Activating Proteins / chemistry
  • GTPase-Activating Proteins / genetics
  • GTPase-Activating Proteins / metabolism*
  • Golgi Matrix Proteins
  • HeLa Cells
  • Humans
  • Membrane Proteins / chemistry
  • Membrane Proteins / metabolism
  • Microfilament Proteins / chemistry
  • Microfilament Proteins / metabolism
  • Phosphate-Binding Proteins
  • Protein Interaction Domains and Motifs
  • Proteins / chemistry
  • Proteins / metabolism
  • trans-Golgi Network / metabolism*

Substances

  • Autoantigens
  • GOLGA4 protein, human
  • GTPase-Activating Proteins
  • Golgi Matrix Proteins
  • Golgi complex autoantigen, 97-kDa
  • Membrane Proteins
  • Microfilament Proteins
  • Phosphate-Binding Proteins
  • Proteins
  • TBC1D23 protein, human
  • WASH protein, human
  • WASHC2C protein, human