Calnexin: a versatile calcium binding integral membrane-bound chaperone of endoplasmic reticulum

Abstract

Calnexin (CNX) is one of the important ubiquitous calcium binding proteins, which was initially identified as an endoplasmic reticulum (ER) type I integral membrane protein. CNX is found from the simplest to the most advanced organisms and acts as a chaperone that share several functions, including Ca²⁺ binding, lectin-like activity, and recognition of misfolded proteins. CNX binds to monoglucosylated carbohydrate on newly-synthesized glycoproteins. CNX together with its team mates, such as ERp57 (a protein disulfide isomerase [PDI]-like protein resident in the ER), and calreticulin (CRT) comprise the so-called "calreticulin/calnexin cycle" which is responsible for the folding of newly synthesized proteins and glycoproteins and for quality control pathways in the endoplasmic reticulum. CNX also contributes to the quality control of non-glycosylated polytopic membrane proteins by binding to misfolded or unassembled transmembrane domains. It also plays a role in the degradation of misfolded proteins. A 3D structure of the soluble, ER luminal part of CNX has been solved. CNX deficiency is not found to be embryonic lethal, however, affects neuronal development and function. Here we describe the historical background, structural and functional aspects of CNX including CNX cycle and ER associated degredation and CNX in plants.