Structure and complex transcription pattern of the mouse SK1 KCa channel gene, KCNN1

Boris E. Shmukler, Chris T. Bond, Sabine Wilhelm, Andrew Bruening-Wright, James Maylie, John P. Adelman, Seth L. Alper

Research output: Contribution to journalArticle

51 Scopus citations

Abstract

Small conductance calcium-gated K+ channels (SK channels) are encoded by the three SK genes, SK1, SK2, and SK3. These channels likely contribute to slow synaptic afterhyperpolarizations of apamin-sensitive and apamin-insensitive types. SK channels are also widely expressed outside the nervous system. The mouse SK1 gene comprises at least 12 exons extending across 19.8 kb of genomic DNA. This gene encodes a complex pattern of alternatively spliced SK1 transcripts widely expressed among mouse tissues. These transcripts exhibit at least four distinct 5′-nucleotide sequence variants encoding at least two N-terminal amino acid sequences. Optional inclusion of exons 7 and 9, together with two alternate splice donor sites in exon 8, yields transcripts encoding eight variant C-terminal amino acid sequences for SK1. These include an altered putative S6 transmembrane span, modification of the C-terminal cytoplasmic domain binding site for calmodulin, and generation of two alternate predicted binding sites for PDZ domain-containing proteins. 20 of the 32 predicted mouse SK1 transcripts are expressed in brain at levels sufficient to allow consistent detection, and encode 16 SK1 polypeptide variants. Only four of these 16 polypeptides preserve the ability to bind calmodulin in a Ca2+-independent manner. Mouse SK1 also exhibits novel, strain-specific, length polymorphism of a polyglutamate repeat in the N-terminal cytoplasmic domain. The evolutionary conservation of this complex transcription pattern suggests a possible role in the tuning of SK1 channel function.

Original languageEnglish (US)
Pages (from-to)36-46
Number of pages11
JournalBiochimica et Biophysica Acta - Gene Structure and Expression
Volume1518
Issue number1-2
DOIs
StatePublished - Mar 19 2001

Keywords

  • Alternate promoter usage
  • Alternate splicing
  • Calcium-gated potassium channel
  • Calmodulin
  • PDZ binding domain
  • Polyglutamate repeat polymorphism
  • RACE

ASJC Scopus subject areas

  • Structural Biology
  • Biophysics
  • Biochemistry
  • Genetics

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