Unlocking Golgi: Why Does Morphology Matter?

Research output: Contribution to journalReview article

Abstract

The mammalian Golgi apparatus is a highly dynamic organelle, which is normally localized in the juxtanuclear space and plays an essential role in the regulation of cellular homeostasis. While posttranslational modification of cargo is mediated by the resident enzymes (glycosyltransferases, glycosidases, and kinases), the ribbon structure of Golgi and its cisternal stacking mostly rely on the cooperation of coiled-coil matrix golgins. Among them, giantin, GM130, and GRASPs are unique, because they form a tripartite complex and serve as Golgi docking sites for cargo delivered from the endoplasmic reticulum (ER). Golgi undergoes significant disorganization in many pathologies associated with a block of the ER-to-Golgi or intra-Golgi transport, including cancer, different neurological diseases, alcoholic liver damage, ischemic stress, viral infections, etc. In addition, Golgi fragments during apoptosis and mitosis. Here, we summarize and analyze clinically relevant observations indicating that Golgi fragmentation is associated with the selective loss of Golgi residency for some enzymes and, conversely, with the relocation of some cytoplasmic proteins to the Golgi. The central concept is that ER and Golgi stresses impair giantin docking site but have no impact on the GM130-GRASP65 complex, thus inducing mislocalization of giantin-sensitive enzymes only. This cardinally changes the processing of proteins by eliminating the pathways controlled by the missing enzymes and by activating the processes now driven by the GM130-GRASP65-dependent proteins. This type of Golgi disorganization is different from the one induced by the cytoskeleton alteration, which despite Golgi de-centralization, neither impairs function of golgins nor alters trafficking.

Original languageEnglish (US)
Pages (from-to)1490-1501
Number of pages12
JournalBiochemistry (Moscow)
Volume84
Issue number12-13
DOIs
Publication statusPublished - Dec 1 2019

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Keywords

  • ER stress
  • GM130
  • GRASP65
  • Golgi morphology
  • Golgi-resident enzymes
  • cancer
  • giantin
  • golgins

ASJC Scopus subject areas

  • Biochemistry

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