Related Experiment Video

Updated: Nov 27, 2025

Molecular Modulation by Lentivirus-Delivered Specific shRNAs in Endoplasmic Reticulum Stressed Neurons
10:50

Molecular Modulation by Lentivirus-Delivered Specific shRNAs in Endoplasmic Reticulum Stressed Neurons

Published on: April 24, 2021

1.2K

Optineurin modulates ER stress-induced signaling pathways and cell death

Gopalakrishna Ramachandran1, Shivranjani C Moharir1, Tirumalai R Raghunand1

  • 1CSIR-Centre for Cellular and Molecular Biology, Hyderabad, 500007, India.

Biochemical and Biophysical Research Communications
|December 4, 2020
PubMed

Insights

The autophagy receptor Optineurin (Optn) plays a key role in protecting cells from endoplasmic reticulum (ER) stress. Optn deficiency increases cell death and alters ER stress signaling pathways, highlighting its protective function.

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Physiology

Background:

  • Endoplasmic reticulum (ER) stress is implicated in various cellular dysfunctions.
  • The role of autophagy receptors in ER stress response requires further elucidation.

Purpose of the Study:

  • To investigate the physiological role of the autophagy receptor Optineurin (Optn) in the cellular response to ER stress.
  • To determine the impact of Optn deficiency on ER stress-induced cell death and signaling pathways.

Main Methods:

  • Utilized cellular models, including Optn-deficient mouse embryonic fibroblasts.
  • Employed animal models (Optn-deficient mice) for in vivo studies.
  • Administered ER stress inducers like tunicamycin and thapsigargin.

Main Results:

  • Optn-deficient cells exhibited significantly higher cell death and caspase-3 activation upon ER stress induction compared to controls.
  • Upregulation of transcript levels for genes in IRE1-XBP1 and PERK-ATF4 pathways was observed in Optn-deficient cells and tissues.
  • Elevated basal levels of IRE1α and PERK were detected in Optn-deficient cells.

Conclusions:

  • Optineurin modulates ER stress-induced signaling pathways, including the IRE1-XBP1 and PERK-ATF4 pathways.
  • Optn provides significant protection against ER stress-induced cell death.
  • Optn is a critical regulator of the cellular response to ER stress.
Keywords:
CytoprotectionER stress ResponseIRE1OptineurinPERK

More Related Videos

Author Spotlight: Exploring the Role of Unfolded Protein Response in HIV-1 Replication and Infectivity10:12

Author Spotlight: Exploring the Role of Unfolded Protein Response in HIV-1 Replication and Infectivity

Published on: June 14, 2024

2.4K
Measurements of Physiological Stress Responses in C. Elegans10:36

Measurements of Physiological Stress Responses in C. Elegans

Published on: May 21, 2020

14.6K

Related Concept Videos

Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.8K
The Unfolded Protein Response01:37

The Unfolded Protein Response

The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
5.9K
Role of ER in the Secretory Pathway01:17

Role of ER in the Secretory Pathway

Eukaryotic cells have a special pathway that enables communication between various intracellular membrane-bound compartments and also with the extracellular environment. This pathway is termed as the secretory pathway.
Components of the secretory pathway
About a third of proteins synthesized in the cell are sorted via the secretory route. They shuffle between different compartments in membrane-bound vesicles until they reach their final destination. The main intracellular compartments involved...
6.5K
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
6.9K
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
7.3K
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
8.9K