Potassium Channels Some Assembly Required

(Shi et al., 1996, and references therein). In the heart Many types of channels and receptors are expressed and the ear, a single-spanning transmembrane protein, in the nervous system, contributing to the complex and minK, coassembles with KvLQT1 tetramers to form a diverse functional repertoires of neurons. Regulation of delayed rectifier that plays an essential role in repolartranscription and translation of the relevant genes exerts ization of the cardiac action potential and in potassium significant control over the phenotype of individual neusecretion in the inner ear. Assembly with minK alters rons. Also important, however, are posttranslational both the gating and permeation properties of KvLQT1 events that regulate the subunit composition of chanchannels (Splawski et al., 1997). In pancreatic b cells nels and receptors, their localization to specialized reand other tissues, including neurons, the sulfonylurea gions of the plasma membrane, and their density on receptor (SUR), a multispanning membrane protein, asthe cell surface. Each of these factors has significant sociates with Kir6.1 or 6.2 pore-forming subunits of the consequences for the functional capabilities and behavinward rectifier family, to form KATP channels (Figure 1B) ioral output of a neuron. (Babenko et al., 1998). SUR, a member of the ATP-bindThis minireview focuses on one such posttranslational ing cassette family of proteins that includes the P glycoevent, the regulation and quality control of subunit asprotein and cystic fibrosis transmembrane conductance sembly during potassium channel biogenesis. Although regulator (CFTR), is important for regulating both the there are a few notable exceptions among channel profunction and trafficking of the KATP channel (Zerangue teins, most membrane proteins, including potassium et al., 1999). channels, fold and assemble in the endoplasmic reticuSequence of Events and Quality Control lum (ER) (Hegde and Lingappa, 1997, and references during K Channel Biogenesis therein). Before transfer to the medial-Golgi compartBiogenesis of a potassium channel involves a complex ment and beyond, these newly minted molecules are series of events. Individual pore-forming subunits are required to pass muster. The ER contains a stringent targeted to the ER membrane and insert, adopting a quality control system that recognizes and retains mismultispanning topology. Compatible subunits assemble folded or incompletely assembled proteins, preventing with each other and with the appropriate auxiliary subtheir transport to locations where aberrant functional units. Along the way, important hydrophilic functional properties could disrupt cellular physiology (Kopito, domains are formed that span the membrane, including 1997, and references therein). The biogenesis of several the pore for potassium conduction and, in voltage-gated types of potassium channels is known to be strictly channels, a charged voltage sensor. The pore contains monitored in the ER (Schulteis et al., 1998; Zerangue et water (Doyle et al., 1998), and there is probably signifial., 1999). cant intrusion of water into the voltage sensor (Papazian After a brief review of the subunit structure and bioand Bezanilla, 1997, and references therein). These hygenesis of potassium channels, this article will describe drophilic structures are presumably shielded from the some recent results concerning two key steps in subunit hydrophobic membrane bilayer in the final, assembled assembly and quality control: the formation of tetramers structure, but there is little information about how these during the biogenesis of voltage-gated potassium chanstructures are generated. Neither is it known whether nels and the formation of octamers during the biogenethese structures form in some protected environment sis of ATP-sensitive potassium (KATP) channels. such as the protein translocation channel (translocon) Potassium channels contain four subunits, which surused for protein import into the ER or in the hydrophobic round a water-filled, K-selective pore (Doyle et al., bilayer itself. 1998). A reentrant loop (the P loop) from each subunit The Shaker potassium channel has been used as a