Bilayer tension-induced clustering of the UPR sensor IRE1

• Author / Creator

  Hossain, Md Zobayer

• The endoplasmic reticulum serves as a center for protein quality control, where chaperones and foldases facilitate protein folding. IRE1 is a transmembrane protein that
  transduces proteotoxic stress signals by forming clusters and activating the unfolded
  protein response (UPR). Recent research indicates that membrane thickness variation
  due to variations in membrane composition drives IRE1 cluster formation, activating
  the UPR even without proteotoxic stress. Based on the stability of the IRE1 dimer,
  we demonstrate a direct relationship between bilayer tension and UPR activation.
  The stability of the IRE1 dimer in a (50%DOPC-50%POPC) membrane at different
  applied bilayer tensions was analyzed via molecular dynamics simulations. For both
  tensed and compressed ER membranes, the potential of mean force for IRE1 dimerization predicts a higher concentration of IRE1 dimers. This study establishes a direct
  biophysical relationship between bilayer tension and UPR activation, demonstrating
  that IRE1 is a mechanosensitive membrane protein

• Subjects / Keywords

  • Bilayer tension
  • UPR
  • ER

• Graduation date

  Fall 2023

• Type of Item

  Thesis

• Degree

  Master of Science

• DOI

  https://doi.org/10.7939/r3-twgx-vp48

• License

  This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.