Related Experiment Video
Updated: Aug 7, 2026

Molecular Modulation by Lentivirus-Delivered Specific shRNAs in Endoplasmic Reticulum Stressed Neurons
Published on: April 24, 2021
Up-regulation of the endoplasmic reticulum molecular chaperone GRP78 during hibernation in thirteen-lined ground
Hapsatou Mamady1, Kenneth B Storey
1Institute of Biochemistry and Department of Biology, College of Natural Sciences, Carleton University, 1125 Colonel By Drive, Ottawa, Ontario, Canada K1S 5B6.
Abstract:
Hibernating mammals endure conditions of low body temperature and oxidative stress that would be highly injurious to humans and most other mammals. Stress conditions frequently trigger the production of molecular chaperones; in the endoplasmic reticulum the glucose-regulated protein-78 (GRP78) helps to minimize protein misfolding under stress. The present study evaluated the GRP78 response in seven organs of hibernating thirteen-lined ground squirrels, Spermophilus tridecemlineatus. Transcript levels of grp78, assessed by RT-PCR, were significantly higher (3.5- to 4.1-fold) in brown adipose tissue and brain of hibernating squirrels compared with euthermic control animals but remained low or stable in all other tissues. GRP78 protein content, assessed by Western blotting, was also elevated in brown adipose and brain during hibernation by 1.4-1.6 fold. A 2490 bp cDNA sequence was retrieved that contained the full length open reading frame of ground squirrel grp78 and the translated protein sequence of 654 amino acids shared 98-99% identity with GRP78 from other mammalian sources. Selected specific amino acid substitutions were found in the ground squirrel sequence that may aid GRP78 function under the near 0 degrees C body temperatures of the hibernating state. Electrophoretic mobility shift and supershift assays showed that the activating transcription factor, ATF4, binds to the promoter region of the grp78 gene in ground squirrel brain and may be responsible for grp78 up-regulation during hibernation. Changes in grp78 gene and protein expression appear to aid stress tolerance in two highly oxygen-dependent organs that are critical to whole animal survival during hibernation.
Related Concept Videos
Regulation of the Unfolded Protein Response
Export of Misfolded Proteins out of the ER
The Unfolded Protein Response
Protein Folding Quality Check in the RER
Protein Modifications in the RER
Broadly, these modifications can be categorized into four main categories — glycosylation, formation of disulfide bonds, assembly of protein subunits, and specific proteolytic cleavages like removal of signal sequences.
Molecular Chaperones and Protein Folding
The...