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Calcium-mediated calreticulin-IRE1α interaction drives dynamic fluctuation of IRE1α activity under chronic endoplasmic reticulum stress - PubMed

7 hours ago
  • #Calcium Signaling
  • #Endoplasmic Reticulum Stress
  • #IRE1α Activity
  • Calcium-mediated interaction between calreticulin and IRE1α drives dynamic fluctuations in IRE1α activity during chronic endoplasmic reticulum (ER) stress.
  • The unfolded protein response (UPR) exhibits an 'up-down-up' fluctuation pattern of IRE1α signal under prolonged ER stress across various cell types.
  • Calreticulin-IRE1α interaction intensity fluctuates and inversely correlates with IRE1α-BIP interaction, which suppresses IRE1α activity.
  • ER luminal Ca2+ concentration shows a 'down-up-down' pattern over time, negatively affecting the calreticulin-IRE1α interaction.
  • Circadian rhythmic fluctuation of calreticulin-IRE1α interaction and IRE1α phosphorylation is observed in mouse liver under physiological conditions.
  • The study suggests a calcium-mediated, calreticulin-driven mechanism for IRE1α activity fluctuation as a cellular adaptation to chronic ER stress.