BOLLO Mariana Ines
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Calcinerurin interacts with PERK to regulate the unfolded protein response (UPR)
BOLLO M, PAREDES RM, HOLSTEIN D., ZHELEZNOVA N, CAMACHO P. AND LECHLEITER, J
Congreso; 16th Symposium on Ca2+ binding proteins and Ca2+ function in health and disease- 16-20 de Noviembre 2009, Pucón, Chile; 2009
CALCINEURINA INTERACTUA CON PERK PARA ALIVIAR EL ESTRES DE RETICULO ENDOPLASMICO (Calcinerurin interacts with PERK to regulate the unfolded protein response (UPR)). 1,3Bollo, M. 1,2Paredes, RM, 2Holstein, D., 1Zheleznova, N. 1Camacho, P. and 2Lechleiter,J. 1Department of Physiology and 2Department of Cellular and Structural Biology, UTHSCSA, 7703 Floyd Curl Drive, 78229-3900, San Antonio, TX, USA 7703 Floyd Curl Drive, 78229-3900, San Antonio, TX, USA 7703 Floyd Curl Drive, 78229-3900, San Antonio, TX, USA 3Instituto de Investigación Médicas MyM Ferreyra, (INIMEC-CONICET), Friuli 2434, 5016, Córdoba, Argentina. The accumulation of misfolded proteins within the endoplasmic reticulum (ER) triggers a cellular process known as the UPR, in which the cell attempts to restore ER homeostasis. The UPR can be triggered by changes in the Ca2+ homeostasis within the organelle. An immediate response is the attenuation of protein translation via autophosphorylation of PERK, which is a type I ER membrane protein. During stress, BIP dissociates from the luminal domain of PERK, leading to dimerization and autophosphorylation. When the cells are unable to re-establish ER homeostasis, an apoptotic response is initiated by an ER specific caspase. In this study, we observed a rise in cytosolic Ca2+ after treatment with the ER stressor tunicamycin and a rapid increase in calcineurin (CN) expression levels during ER stress. Data obtained from co-immunoprecipitation, pull down and in vitro kinase assays, demonstrate that CN associates with the cytosolic domain of PERK, promoting its auto-phosphorylation and further attenuating protein translation. Data obtained in vivo indicate that knockdown of CN predisposes cells to delay induction of apoptotic signaling. Together, these data suggest a central role for CN in the early UPR.