Luminal Ca2+ depletion during the unfolded protein response in Xenopus oocytes: Cause and consequence

• Autores: Paredes, R. Madelaine; Bollo, Mariana Ines; Holstein, Deborah; Lechleiter, James D.
• Año de publicación: 2013
• Idioma: inglés
• Tipo de recurso: artículo
• Materia: Er Stress; Calcium Signalling; Tunycamicin; Thapsigargin
• Institución: Consejo Nacional de Investigaciones Científicas y Técnicas

The endoplasmic reticulum (ER) is a Ca2+ storing organelle that plays a critical role in the synthesis, folding and post-translational modifications of many proteins. The ER enters into a condition of stress when the load of newly synthesized proteins exceeds its folding and processing capacity. This activates a signal transduction pathway called the unfolded protein response (UPR) that attempts to restore homeostasis. The precise role of ER Ca2+ in the initiation of the UPR has not been defined. Specifically, it has not been established whether ER Ca2+ dysregulation is a cause or consequence of ER stress. Here, we report that partial depletion of ER Ca2+ stores induces a significant induction of the UPR, and leads to the retention of a normally secreted protein Carboxypeptidase Y. Moreover, inhibition of protein glycosylation by tunicamycin rapidly induced an ER Ca2+ leak into the cytosol. However, blockade of the translocon with emetine inhibited the tunicamycin-induced Ca2+ release. Furthermore, emetine treatment blocked elF2α phosphorylation and reduced expression of the chaperone BiP. These findings suggest that Ca2+ may be both a cause and a consequence of ER protein misfolding. Thus, it appears that ER Ca2+ leak is a significant co-factor for the initiation of the UPR.
Fil: Paredes, R. Madelaine. University of Texas; Estados Unidos
Fil: Bollo, Mariana Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina
Fil: Holstein, Deborah. University of Texas; Estados Unidos
Fil: Lechleiter, James D.. University of Texas; Estados Unidos