Optineurin modulates ER stress-induced signaling pathways and cell death

Gopalakrishna Ramachandran; Shivranjani C Moharir; Tirumalai R Raghunand; Ghanshyam Swarup

doi:10.1016/j.bbrc.2020.11.091

Optineurin modulates ER stress-induced signaling pathways and cell death

Biochem Biophys Res Commun. 2021 Jan 1:534:297-302. doi: 10.1016/j.bbrc.2020.11.091. Epub 2020 Dec 1.

Authors

Gopalakrishna Ramachandran¹, Shivranjani C Moharir¹, Tirumalai R Raghunand¹, Ghanshyam Swarup²

Affiliations

¹ CSIR-Centre for Cellular and Molecular Biology, Hyderabad, 500007, India.
² CSIR-Centre for Cellular and Molecular Biology, Hyderabad, 500007, India. Electronic address: [email protected].

PMID: 33272572
DOI: 10.1016/j.bbrc.2020.11.091

Abstract

We have investigated the physiological role of the autophagy receptor Optineurin/Optn in endoplasmic reticulum (ER) stress response using cellular and animal models. In comparison to their normal counterparts, Optn-deficient mouse embryonic fibroblasts showed significantly higher cell death and caspase-3 activation upon treatment with tunicamycin and thapsigargin, inducers of ER stress. The transcript levels of some of the genes regulated by the IRE1-XBP1 and PERK-ATF4 pathways were upregulated in Optn-deficient cells, in comparison with normal cells, upon treatment with tunicamycin, and also in the brain cortex and liver of tunicamycin treated Optn-deficient mice. Also, the basal levels of IRE1α and PERK were higher in Optn-deficient cells. These results suggest that Optn modulates ER stress-induced signaling pathways and provides protection from ER stress-induced cell death.

Keywords: Cytoprotection; ER stress Response; IRE1; Optineurin; PERK.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Autophagy / physiology
Cell Cycle Proteins / deficiency
Cell Cycle Proteins / genetics
Cell Cycle Proteins / physiology*
Cell Death / physiology
Cells, Cultured
Endoplasmic Reticulum Stress / genetics
Endoplasmic Reticulum Stress / physiology*
Endoribonucleases / genetics
Endoribonucleases / metabolism
Fibroblasts / cytology
Fibroblasts / physiology
Gene Expression
Membrane Transport Proteins / deficiency
Membrane Transport Proteins / genetics
Membrane Transport Proteins / physiology*
Mice
Mice, Knockout
Protein Serine-Threonine Kinases / genetics
Protein Serine-Threonine Kinases / metabolism
RNA, Messenger / genetics
RNA, Messenger / metabolism
Signal Transduction / physiology
Unfolded Protein Response / genetics
eIF-2 Kinase / genetics
eIF-2 Kinase / metabolism

Substances

Cell Cycle Proteins
Membrane Transport Proteins
Optn protein, mouse
RNA, Messenger
Ern1 protein, mouse
PERK kinase
Protein Serine-Threonine Kinases
eIF-2 Kinase
Endoribonucleases