Calreticulin: one protein, one gene, many functions

TLDR

The endoplasmic reticulum is essential for protein synthesis and chaperoning, stores and releases Ca²⁺, and houses the unique luminal protein calreticulin, which influences numerous cellular functions both inside and outside the ER. In the ER lumen, calreticulin acts as a chaperone and regulates Ca²⁺ homeostasis, while also modulating ER Ca²⁺ storage and transport to influence intracellular Ca²⁺ dynamics. Calreticulin functions as a versatile lectin‑like chaperone during the synthesis of ion channels, surface receptors, integrins, and transporters, and its activity underscores the dynamic nature of the ER membrane in regulating diverse cellular processes.

Abstract

The endoplasmic reticulum (ER) plays a critical role in the synthesis and chaperoning of membrane-associated and secreted proteins. The membrane is also an important site of Ca2+ storage and release. Calreticulin is a unique ER luminal resident protein. The protein affects many cellular functions, both in the ER lumen and outside of the ER environment. In the ER lumen, calreticulin performs two major functions: chaperoning and regulation of Ca2+ homoeostasis. Calreticulin is a highly versatile lectin-like chaperone, and it participates during the synthesis of a variety of molecules, including ion channels, surface receptors, integrins and transporters. The protein also affects intracellular Ca2+ homoeostasis by modulation of ER Ca2+ storage and transport. Studies on the cell biology of calreticulin revealed that the ER membrane is a very dynamic intracellular compartment affecting many aspects of cell physiology.