Assembly, post-translational processing, and subcellular localization of ion channels

Abstract

Abstract Most ion channels are complex, multi-subunit transmembrane proteins (1-3). Aconsequence of this structural complexity is that the correct functional expression of ion channels requires a diverse series of post-translational events including covalent modifications and subunit oligomerization. After protein synthesis and translocation into the endoplasmic reticulum (ER) membrane, newly-synthesized transmembrane polypeptides may undergo a variety of post-translational modifications (such as proteolytic cleavage, phosphorylation, glycosylation, fatty acylation, and disulphide bond formation). Individual polypeptides must also fold correctly into their native conformation and, in many cases, multiple polypeptide subunits must be accurately assembled into multi-subunit ion-channel complexes. Finally, the modified and assembled ion channels must be delivered to their appropriate subcellular location. Clearly, these subunit folding and oligomerization events must be carried out with great accuracy if ion channels are to perform their appropriate physiological function. How the processing, assembly, and subcellular localization of ion channels is achieved with sufficient accuracy is clearly of great interest and significance and has been the subject of a great deal of recent research.