Post-ER Stress Biogenesis of Golgi Is Governed by Giantin

Cole P. Frisbie, Alexander Y. Lushnikov, Alexey V. Krasnoslobodtsev, Jean Jack M. Riethoven, Jennifer L. Clarke, Elena I. Stepchenkova, Armen Petrosyan

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND: The Golgi apparatus undergoes disorganization in response to stress, but it is able to restore compact and perinuclear structure under recovery. This self-organization mechanism is significant for cellular homeostasis, but remains mostly elusive, as does the role of giantin, the largest Golgi matrix dimeric protein. METHODS: In HeLa and different prostate cancer cells, we used the model of cellular stress induced by Brefeldin A (BFA). The conformational structure of giantin was assessed by proximity ligation assay and atomic force microscopy. The post-BFA distribution of Golgi resident enzymes was examined by 3D SIM high-resolution microscopy. RESULTS: We detected that giantin is rather flexible than an extended coiled-coil dimer and BFA-induced Golgi disassembly was associated with giantin monomerization. A fusion of the nascent Golgi membranes after BFA washout is forced by giantin re-dimerization via disulfide bond in its luminal domain and assisted by Rab6a GTPase. GM130-GRASP65-dependent enzymes are able to reach the nascent Golgi membranes, while giantin-sensitive enzymes appeared at the Golgi after its complete recovery via direct interaction of their cytoplasmic tail with N-terminus of giantin. CONCLUSION: Post-stress recovery of Golgi is conducted by giantin dimer and Golgi proteins refill membranes according to their docking affiliation rather than their intra-Golgi location.

Original languageEnglish (US)
JournalCells
Volume8
Issue number12
DOIs
StatePublished - Dec 13 2019

Keywords

  • Brefeldin A
  • GRASP65
  • Golgi biogenesis
  • Rab6a
  • giantin

ASJC Scopus subject areas

  • Medicine(all)

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