Calreticulin signaling in health and disease

Calreticulin is an endoplasmic reticulum Ca2+ binding chaperone that has multiple functions inside and outside of the endoplasmic reticulum. It is involved in the quality control of newly synthesized proteins and glycoproteins, interacting with various other endoplasmic reticulum chaperones, specifically calnexin and ER protein of 57-kDa in the calreticulin/calnexin cycle. Calreticulin also plays a crucial role in regulating intracellular Ca2+ homeostasis, associating calreticulin with a wide variety of signaling processes, such as cardiogenesis, adipocyte differentiation and cellular stress responses. The role of calreticulin outside of the endoplasmic reticulum is also extensive, including functions in wound healing and immunity. Therefore, calreticulin has important implications in health and disease.Signaling facts-Calreticulin controls calcineurin activity and NF-AT- and MEF2C-dependent expression of cardiac genes through InsP3R mediated ER Ca2+ release.-Calreticulin deficiency up-regulates the CAMKII-dependent signaling pathway.-Calreticulin over-expression decreases adipogenic factors (lipoprotein lipase, αP2, PPAR and C/EBPα).-Cell surface calreticulin signals pre-apoptotic cellular clearance by binding to LDL-receptor-related protein (LRP) on phagocytes.