A novel isoform of SK2 assembles with other SK subunits in mouse brain

Timothy Strassmaier, Chris T. Bond, Claudia A. Sailer, Hans Guenther Knaus, James Maylie, John Adelman

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

The SK2 subtype of small conductance Ca2+-activated K + channels is widely distributed throughout the central nervous system and modulates neuronal excitability by contributing to the afterhyperpolarization that follows an action potential. Western blots of brain membrane proteins prepared from wild type and SK2-null mice reveal two isoforms of SK2, a 49-kDa band corresponding to the previously reported SK2 protein (SK2-S) and a novel 78-kDa form. Complementary DNA clones from brain and Western blots probed with an antibody specific for the longer form, SK2-L, identified the larger molecular weight isoform as an N-terminally extended SK2 protein. The N-terminal extension of SK2-L is cysteine-rich and mediates disulfide bond formation between SK2-L subunits or with heterologous proteins. Immunohistochemistry revealed that in brain SK2-L and SK2-S are expressed in similar but not identical patterns. Heterologous expression of SK2-L results in functional homomeric channels with Ca2+ sensitivity similar to that of SK2-S, consistent with their shared core and intracellular C-terminal domains. In contrast to the diffuse, uniform surface distribution of SK2-S, SK2-L channels cluster into sharply defined, distinct puncta suggesting that the extended cysteine-rich N-terminal domain mediates this process. Immunoprecipitations from transfected cells and mouse brain demonstrate that SK2-L co-assembles with the other SK subunits. Taken together, the results show that the SK2 gene encodes two subunit proteins and suggest that native SK2-L subunits may preferentially partition into heteromeric channel complexes with other SK subunits.

Original languageEnglish (US)
Pages (from-to)21231-21236
Number of pages6
JournalJournal of Biological Chemistry
Volume280
Issue number22
DOIs
StatePublished - Jun 3 2005

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Brain
Protein Isoforms
Cysteine
Western Blotting
L Forms
Calcium-Activated Potassium Channels
Proteins
Protein S
Protein Subunits
Neurology
Immunoprecipitation
Disulfides
Action Potentials
Membrane Proteins
Central Nervous System
Complementary DNA
Clone Cells
Genes
Molecular Weight
Immunohistochemistry

ASJC Scopus subject areas

  • Biochemistry

Cite this

Strassmaier, T., Bond, C. T., Sailer, C. A., Knaus, H. G., Maylie, J., & Adelman, J. (2005). A novel isoform of SK2 assembles with other SK subunits in mouse brain. Journal of Biological Chemistry, 280(22), 21231-21236. https://doi.org/10.1074/jbc.M413125200

A novel isoform of SK2 assembles with other SK subunits in mouse brain. / Strassmaier, Timothy; Bond, Chris T.; Sailer, Claudia A.; Knaus, Hans Guenther; Maylie, James; Adelman, John.

In: Journal of Biological Chemistry, Vol. 280, No. 22, 03.06.2005, p. 21231-21236.

Research output: Contribution to journalArticle

Strassmaier, T, Bond, CT, Sailer, CA, Knaus, HG, Maylie, J & Adelman, J 2005, 'A novel isoform of SK2 assembles with other SK subunits in mouse brain', Journal of Biological Chemistry, vol. 280, no. 22, pp. 21231-21236. https://doi.org/10.1074/jbc.M413125200
Strassmaier, Timothy ; Bond, Chris T. ; Sailer, Claudia A. ; Knaus, Hans Guenther ; Maylie, James ; Adelman, John. / A novel isoform of SK2 assembles with other SK subunits in mouse brain. In: Journal of Biological Chemistry. 2005 ; Vol. 280, No. 22. pp. 21231-21236.
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