Post-ER Stress Biogenesis of Golgi Is Governed by Giantin

Authors

• Cole P. Frisbie, University of Nebraska Medical CenterFollow
• Alexander Y. Lushnikov, University of Nebraska Medical CenterFollow
• Alexey V. Krasnoslobodtsev, University of Nebraska Medical CenterFollow
• Jean-Jack Riethoven, University of Nebraska - LincolnFollow
• Jennifer L. Clarke, University of Nebraska-LincolnFollow
• Elena I. Stepchenkova, Russian Academy of SciencesFollow
• Armen Petrosyan, University of Nebraska Medical CenterFollow

ORCID IDs

Alexey V. Krasnoslobodtsev

Jean-Jack M. Riethoven

Jennifer L. Clarke

Elena I. Stepchenkova

Armen Petrosyan

Document Type

Article

Date of this Version

2019

Citation

Cells 2019, 8, 1631

Comments

© 2019 by the authors.

Open access

doi:10.3390/cells8121631

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.