title: Alternatively spliced domains interact to regulate BK potassium channel gating.
abstract: Most human genes contain multiple alternative splice sites believed to extend the complexity and diversity of the proteome. However, little is known about how interactions among alternative exons regulate protein function. We used the Caenorhabditis elegans slo-1 large-conductance calcium and voltage-activated potassium (BK) channel gene, which contains three alternative splice sites (A, B, and C) and encodes at least 12 splice variants, to investigate the functional consequences of alternative splicing. These splice sites enable the insertion of exons encoding part of the regulator of K(+) conductance (RCK)1 Ca(2+) coordination domain (exons A1 and A2) and portions of the RCK1-RCK2 linker (exons B0, B1, B2, C0, and C1). Exons A1 and A2 are used in a mutually exclusive manner and are 67% identical. The other exons can extend the RCK1-RCK2 linker by up to 41 residues. Electrophysiological recordings of all isoforms show that the A1 and A2 exons regulate activation kinetics and Ca(2+) sensitivity, but only if alternate exons are inserted at site B or C. Thus, RCK1 interacts with the RCK1-RCK2 linker, and the effect of exon variation on gating depends on the combination of alternate exons present in each isoform.
authors: Department of Molecular and Cellular Physiology, Stanford University, Stanford, CA 94305, USA.
authors: Brandon E
authors: BE
authors: Johnson
authors: Dominique A
authors: DA
authors: Glauser
authors: Elise S
authors: ES
authors: Dan-Glauser
authors: D Brent
authors: DB
authors: Halling
authors: Richard W
authors: RW
authors: Aldrich
authors: Miriam B
authors: MB
authors: Goodman
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D001703:Biophysics / Q000379:methods; D017173:Caenorhabditis elegans; D004594:Electrophysiology / Q000379:methods; D005091:Exons; D014644:Genetic Variation; D007700:Kinetics; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000737:chemistry* / Q000378:metabolism; D008957:Models, Genetic; D009865:Oocytes / Q000378:metabolism; D017434:Protein Structure, Tertiary; D014981:Xenopus / Q000378:metabolism
chemical_list: D051036:Large-Conductance Calcium-Activated Potassium Channels