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

Jonathan V Reddy1, Alondra Schweizer Burguete, Khambhampaty Sridevi

  • 1Department of Biochemistry, Stanford University School of Medicine, Stanford, CA 94305-5307, USA.

Insights

GCC185 is essential for recycling mannose 6-phosphate receptors (MPRs) from endosomes to the Golgi. This Golgin protein acts as a Rab9 effector, ensuring proper MPR transport and preventing their degradation.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Protein Trafficking

Background:

  • Mannose 6-phosphate receptors (MPRs) are crucial for delivering lysosomal enzymes to endosomes.
  • MPR recycling to the Golgi involves Rab9 GTPase and its effector TIP47.
  • The precise mechanism of Rab9-bearing vesicle docking at the trans-Golgi network (TGN) remains unclear.

Purpose of the Study:

  • To investigate the role of GCC185 in MPR recycling.
  • To determine if GCC185 functions as a Rab9 effector in MPR transport.
  • To elucidate the mechanism of vesicle docking at the TGN.

Main Methods:

  • Cell-based assays in living cells.
  • In vitro binding and transport assays.
  • Depletion of GCC185 using RNA interference.

Main Results:

  • GCC185 is identified as a Rab9 effector required for MPR recycling.
  • GCC185 mediates the docking of Rab9-bearing vesicles at the TGN.
  • Loss of GCC185 leads to increased MPR degradation and hexosaminidase secretion.

Conclusions:

  • GCC185 plays a critical role in the retrograde transport of MPRs.
  • GCC185 acts as a specific tethering factor for late endosome-to-TGN transport vesicles.
  • This study assigns a function to GCC185 in the MPR pathway.

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