BOLLO Mariana Ines
congresos y reuniones científicas
Calcium signaling stimulates PERK pathway
Congreso; Reunión Anual de la Sociedad Argentina de Investigación en Neurociencias; 2019
Institución organizadora:
Reunión Anual de la Sociedad Argentina de Investigación en Neurociencias
The endoplasmic reticulum (ER) plays a critical role in a variety of processes, where Ca2+ acts a key messenger. It is well know that the accumulation of unfolded proteins into the organelle, activates a signal transduction cascade called Unfolded Protein Response (UPR). The immediate response, which attempts to restore homeostasis, is the attenuation of protein synthesis due to the phosphorylation of eIF2α, by activation of PERK, a ER transmembrane kinase. We demonstrated that Calcineurin (CN) directly interacts with PERK increasing its activation. Also, we observed in astrocytes that the isoform β of CN (CNAβ-B) has a cytoprotective effect dependent on PERK. In addition we detected Ca2+ ER efflux increase through the translocon during acute phase of UPR. Although the involvement of Ca2+ signaling in a multitude of cellular pathways has been well documented, little is known about its role in restoring homeostasis, once UPR is activated. Here, we evaluated the dependence of Ca2+ on PERK and eIF2α phosphorylation by immunoprecipitations, Western Blots and immunocitochemestry. Also was .analyzed PERK/CNAβ-B interaction, after induces stress and pharmacologically modify translocon activity. . The effect of ER Ca2+ efflux on PERK activation was further studied using a cell line knock out for the 3 isoforms of the IP3 receptor (HEK IP3Rc TKO). Overall these data strongly suggest that PERK is activated by Ca2+ signal originated through the translocon during acute phase of ER stress.