Proteins and chemical chaperones involved in neuronal nicotinic receptor expression and function: An update

Neuronal nicotinic ACh receptors (nAChRs) are a family of ACh-gated cation channels, and their homeostasis or proteostasis is essential for the correct physiology of the central and peripheral nervous systems. The proteostasis network regulates the folding, assembly, degradation and trafficking of nAChRs in order to ensure their efficient and functional expression at the cell surface. However, as nAChRs are multi-subunit, multi-span, integral membrane proteins, the folding and assembly is a very inefficient process, and only a small proportion of subunits can form functional pentamers. Moreover, the efficiency of assembly and trafficking varies widely depending on the nAChR subtypes and the cell type in which they are expressed. A detailed understanding of the mechanisms that regulate the functional expression of nAChRs in neurons and non-neuronal cells is therefore important. The purpose of this short review is to describe more recent findings concerning the chaperone proteins and target-specific and target-nonspecific pharmacological chaperones that modulate the expression of nAChR subtypes, and the possible mechanisms that underlie the dynamic changes of cell surface nAChRs.