Regulation of protein glycosylation and sorting by the Golgi matrix proteins GRASP55/65

Nat Commun. 2013:4:1659. doi: 10.1038/ncomms2669.

Abstract

The Golgi receives the entire output of newly synthesized cargo from the endoplasmic reticulum, processes it in the stack largely through modification of bound oligosaccharides, and sorts it in the trans-Golgi network. GRASP65 and GRASP55, two proteins localized to the Golgi stack and early secretory pathway, mediate processes including Golgi stacking, Golgi ribbon linking and unconventional secretion. Previously, we have shown that GRASP depletion in cells disrupts Golgi stack formation. Here we report that knockdown of the GRASP proteins, alone or combined, accelerates protein trafficking through the Golgi membranes but also has striking negative effects on protein glycosylation and sorting. These effects are not caused by Golgi ribbon unlinking, unconventional secretion or endoplasmic reticulum stress. We propose that GRASP55/65 are negative regulators of exocytic transport and that this slowdown helps to ensure more complete protein glycosylation in the Golgi stack and proper sorting at the trans-Golgi network.

Publication types

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

MeSH terms

  • Cathepsin D / metabolism
  • Glycosylation
  • Golgi Apparatus / enzymology
  • Golgi Apparatus / metabolism*
  • Golgi Matrix Proteins
  • Humans
  • Integrins / metabolism*
  • Membrane Proteins / metabolism*
  • Protein Transport*

Substances

  • GORASP1 protein, human
  • GORASP2 protein, human
  • Golgi Matrix Proteins
  • Integrins
  • Membrane Proteins
  • Cathepsin D