GORAB scaffolds COPI at the trans-Golgi for efficient enzyme recycling and correct protein glycosylation

Research output: Contribution to journalArticle

  • External authors:
  • Tomasz Maciej Witkos
  • Wing Lee Chan
  • Merja Joensuu
  • Ed Pallister
  • Jane Thomas-Oates
  • Christophe Biot
  • Yann Guerardel
  • Willy Morelle
  • Daniel Ungar
  • Felix T. Wieland
  • Eija Jokitalo
  • Mayada Tassabehji
  • Uwe Kornak

Abstract

COPI is a key mediator of protein trafficking within the secretory pathway. COPI
is recruited to the membrane primarily through binding to Arf GTPases, upon
which it undergoes assembly to form coated transport intermediates responsible
for trafficking numerous proteins, including Golgi-resident enzymes. Here, we
identify GORAB, the protein mutated in the skin and bone disorder gerodermia
osteodysplastica, as a component of the COPI machinery. GORAB forms stable
domains at the trans-Golgi that, via interactions with the COPI-binding protein
Scyl1, promote COPI recruitment to these domains. Pathogenic GORAB
mutations perturb Scyl1 binding or GORAB assembly into domains, indicating
the importance of these interactions. Loss of GORAB causes impairment of COPI mediated retrieval of trans-Golgi enzymes, resulting in a deficit in glycosylation
of secretory cargo proteins. Our results therefore identify GORAB as a COPI
scaffolding factor, and support the view that defective protein glycosylation is
major disease mechanism in gerodermia osteodysplastica.

Bibliographical metadata

Original languageEnglish
JournalNat Commun
DOIs
Publication statusPublished - 10 Jan 2019

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