Mammalian central neurons express a large number of different voltage-dependent K+ (Kv) channel complexes with diverse patterns of cellular expression and subcellular localization that impact their contribution to regulating cell excitability. This chapter reviews the mechanisms regulating intracellular trafficking and localization of Kv channels in mammalian neurons. Kv channels function as supramolecular protein complexes composed of four pore-forming and voltage-sensing principal (or α) subunits, plus up to four associated auxiliary (or β) subunits. These channels can also associate with various scaffolding proteins and enzymes, which can impact channel localization, turnover, and function. As such, the functional characteristics, abundance, and subcellular localization of Kv channel complexes are determined by diverse protein-protein interactions, both between constituent α and β subunits as well as between these subunits and a wide variety of interacting proteins. Expression of Kv channel genes is highly regulated. Mechanisms that regulate channel assembly, folding, and ER export of Kv channels are beginning to be understood. Endoplasmic reticulum (ER) export competence seems to be determined by two major mechanisms: the chaperone-based quality control machinery that senses and acts on the folding state of proteins while in the ER, and the machinery that recognizes specific trafficking determinants. Specific intracellular mechanisms also exist to sort newly synthesized Kv channels into axon- or dendrite-destined transport vesicles.
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)