Shaker encodes a family of putative potassium channel proteins in the nervous system of Drosophila.

Abstract

The Shaker locus of Drosophila contains a very large transcription unit. It is expressed predominantly in the nervous system by multiple, differential as well as alternative, splicing mechanisms into different, but functionally related proteins. The structure of the Shaker transcription unit and the properties of the encoded Shaker protein family provide a molecular basis for A channel diversity in excitable cells.

Potassium channels expressed from rat brain cDNA have delayed rectifier properties

“…Currents carried by these channels have been separated into voltage-gated currents, such as the delayed rectifier, anomalous rectifier and transient (Ig) currents, and ligndgated currents, such as Ca2+-activated and ATPsensitive currents. Recent studies using recombinant DNA techniques indicate that in Drosophila melanogaster the Shaker gene complex encodes a family of K ÷ channels [1][2][3] with functional properties similar to the channels that mediate the transient, rapidly inactivating IA current observed in a variety of cell types in different species [4,5]. Using a low stringency hybridization protocol with a Drosophila Shaker cDNA probe a homologous cDNA, named RCK1, was isolated from a rat cerebral cortex library [6].…”

Alternative Splicing in the Pore-Forming Region ofshakerPotassium Channels

“…In Drosophila, the transient K ϩ current is generated by the shak er and shal members of the Shak er family of potassium channels (Wu and Haugland, 1985;Papazian et al, 1987;Iverson et al, 1988;Kamb et al, 1988;Pongs et al, 1988;Timpe et al, 1988;Stocker et al, 1990;Wei et al, 1990). The Drosophila shaker subfamily transcript undergoes alternative splicing at the 5Ј and 3Ј ends of the coding region, with five alternative 5Ј ends and two alternative 3Ј ends (Kamb et al, 1988;Pongs et al, 1988;Schwarz et al, 1988).…”

“…The Drosophila shaker subfamily transcript undergoes alternative splicing at the 5Ј and 3Ј ends of the coding region, with five alternative 5Ј ends and two alternative 3Ј ends (Kamb et al, 1988;Pongs et al, 1988;Schwarz et al, 1988). This alternative splicing generates up to 10 different proteins that form markedly different ion channel types, from rapidly inactivating A-type currents to slowly or noninactivating delayed rectifier-type currents.…”

“…Functional channels are composed of tetramers of shaker proteins (Isacoff et al, 1990;MacKinnon, 1991), and heteromers can also be produced between the alternate splice forms of shaker, generating further diversity in channel types (Isacoff et al, 1990;McCormack et al, 1990;Ruppersberg et al, 1990;MacKinnon, 1991;Sheng et al, 1993;Wang et al, 1993). In Drosophila, all of these splice variants share a common conserved core region, which extends from before the first transmembrane region (S1) to the end of the pore-forming P region (Kamb et al, 1988;Pongs et al, 1988;Schwarz et al, 1988). Ion flux occurs through the P region, and site-directed mutagenesis of the amino acid sequence of this region has important functional consequences (MacKinnon et al, 1988;MacKinnon and Miller, 1989;MacKinnon and Yellen, 1990;Hartmann et al, 1991;Yellen et al, 1991;Yool and Schwarz, 1991;Heginbotham and MacKinnon, 1992).…”

The selectivity filter of a ligand‐gated ion channel

“…Recently several ion channel proteins of both types have been cloned and sequenced, e.g. voltagedependent sodium [2], potassium [3,4] and calcium [5] channels and ligand-gated nicotinic acetylcholine receptors 161, GABAA [7] and one subunit of the glycine receptors [8]. The sequence data provided by recombinant DNA techniques were supplemented by sitedirected mutagenesis experiments, electrophysiological, ultrastructural (EM) and biochemical data.…”