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Calreticulin, Ca2+, and calcineurin - signaling from the endoplasmic reticulum Groenendyk J; Lynch J; Michalak MMol Cells 2004[Jun]; 17 (3): 383-9Calcium (Ca2+) is a universal signalling molecule involved in many aspects of cellular function. The majority of intracellular Ca2+ is stored in the endoplasmic reticulum and once Ca2+ is released from the endoplasmic reticulum, specific plasma membrane Ca2+ channels are activated, resulting in increased intracellular Ca2+. In the lumen of the endoplasmic reticulum, Ca2+ is buffered by Ca2+ binding chaperones such as calreticulin. Calreticulin-deficiency is lethal in utero due to impaired cardiac development and in the absence of calreticulin, Ca2+ storage capacity within the endoplasmic reticulum and inositol 1,4,5-trisphosphate (InsP3) receptor mediated Ca2+ release from the endoplasmic reticulum are compromised. Over-expression of constitutively active calcineurin in the heart rescues calreticulin-deficient mice from embryonic lethality. This observation indicates that calreticulin is a key upstream regulator of calcineurin in Ca2+-signalling pathways and highlights the importance of the endoplasmic reticulum and endoplasmic reticulum-dependent Ca2+ homeostasis for cellular commitment and tissue development during organogenesis. Furthermore, Ca2+ handling by the endoplasmic reticulum has profound effects on cell sensitivity to apoptosis. Signalling between calreticulin in the lumen of the endoplasmic reticulum and calcineurin in the cytoplasm may play a role in the modulation of cell sensitivity to apoptosis and the regulation of Ca2+-dependent apoptotic pathways.|Animals[MESH]|Apoptosis/physiology[MESH]|Calcineurin/*metabolism[MESH]|Calcium Channels/metabolism[MESH]|Calcium Signaling/*physiology[MESH]|Calcium/*metabolism[MESH]|Calreticulin/*metabolism[MESH]|Endoplasmic Reticulum/*metabolism[MESH]|Inositol 1,4,5-Trisphosphate/metabolism[MESH]|Mice[MESH]|Myocardium/metabolism[MESH] |
