Calmodulin Regulates Assembly and Trafficking of SK4/IK1 Ca 2+-activated K+ Channels

William J. Joiner, Rajesh Khanna, Lyanne C. Schlichter, Leonard K. Kaczmarek

Research output: Contribution to journalArticle

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Abstract

Calmodulin (CaM) regulates gating of several types of ion channels but has not been implicated in channel assembly or trafficking. For the SK4/IK1 K + channel, CaM bound to the proximal C terminus ("Ct1" domain) acts as the Ca2+ sensor. We now show that CaM interacting with the C terminus of SK4 also controls channel assembly and surface expression. In transfected cells, removing free CaM by overexpressing the CaM-binding domain, Ct1, redistributed full-length SK4 protein from the plasma membrane to the cytoplasm and decreased whole-cell currents. Making more CaM protein available by overexpressing the CaM gene abrogated the dominant-negative effect of Ct1 and restored both surface expression of SK4 protein and whole-cell currents. The distal C-terminal domain ("Ct2") also plays a role in assembly, but is not CaM-dependent. Co-immunoprecipitation experiments demonstrated that multimerization of SK4 subunits was enhanced by CaM and inhibited by removal of CaM, indicating that CaM regulates trafficking of SK4 by affecting the assembly of channels. Our results support a model in which CaM-dependent association of SK4 monomers at their Ct1 domains regulates channel assembly and surface expression. This appears to represent a novel mechanism for controlling ion channels, and consequently, the cellular functions that depend on them.

Original languageEnglish (US)
Pages (from-to)37980-37985
Number of pages6
JournalJournal of Biological Chemistry
Volume276
Issue number41
StatePublished - Oct 12 2001
Externally publishedYes

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Calmodulin
Ion Channels
Ion Channel Gating
Dominant Genes
Proteins
Cell membranes
Immunoprecipitation
Cytoplasm
Genes
Monomers
Cell Membrane

ASJC Scopus subject areas

  • Biochemistry

Cite this

Joiner, W. J., Khanna, R., Schlichter, L. C., & Kaczmarek, L. K. (2001). Calmodulin Regulates Assembly and Trafficking of SK4/IK1 Ca 2+-activated K+ Channels. Journal of Biological Chemistry, 276(41), 37980-37985.

Calmodulin Regulates Assembly and Trafficking of SK4/IK1 Ca 2+-activated K+ Channels. / Joiner, William J.; Khanna, Rajesh; Schlichter, Lyanne C.; Kaczmarek, Leonard K.

In: Journal of Biological Chemistry, Vol. 276, No. 41, 12.10.2001, p. 37980-37985.

Research output: Contribution to journalArticle

Joiner, WJ, Khanna, R, Schlichter, LC & Kaczmarek, LK 2001, 'Calmodulin Regulates Assembly and Trafficking of SK4/IK1 Ca 2+-activated K+ Channels', Journal of Biological Chemistry, vol. 276, no. 41, pp. 37980-37985.
Joiner, William J. ; Khanna, Rajesh ; Schlichter, Lyanne C. ; Kaczmarek, Leonard K. / Calmodulin Regulates Assembly and Trafficking of SK4/IK1 Ca 2+-activated K+ Channels. In: Journal of Biological Chemistry. 2001 ; Vol. 276, No. 41. pp. 37980-37985.
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