Calmodulin Regulates Assembly and Trafficking of SK4/IK1 Ca2+-activated K+ Channels
Open Access
- 1 October 2001
- journal article
- Published by American Society for Biochemistry & Molecular Biology (ASBMB) in Journal of Biological Chemistry
- Vol. 276 (41), 37980-37985
- https://doi.org/10.1074/jbc.m104965200
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 ofCt1 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.Keywords
This publication has 39 references indexed in Scilit:
- Calcium-activated Potassium Channels Sustain Calcium Signaling in T LymphocytesPublished by Elsevier BV ,2001
- Control of Electrical Activity in Central Neurons by Modulating the Gating of Small Conductance Ca2+-activated K+ ChannelsPublished by Elsevier BV ,2001
- Up-regulation of the IKCa1 Potassium Channel during T-cell ActivationPublished by Elsevier BV ,2000
- Calcium‐Activated Potassium Currents In Mammalian NeuronsClinical and Experimental Pharmacology and Physiology, 2000
- hSK4/hIK1, a Calmodulin-binding KCa Channel in Human T LymphocytesPublished by Elsevier BV ,1999
- Bicarbonate and Chloride Secretion in Calu-3 Human Airway Epithelial CellsThe Journal of general physiology, 1999
- cDNA Cloning and Functional Characterization of the Mouse Ca2+-gated K+ Channel, mIK1Published by Elsevier BV ,1998
- Ca2+-activated K+ currents in neurones: types, physiological roles and modulationTrends in Neurosciences, 1996
- Intracellular Ca2+ Signaling Induced by Osmotic Shock in Human T LymphocytesExperimental Cell Research, 1994
- Pharmacological and physiological properties of the after‐hyperpolarization current of bullfrog ganglion neurones.The Journal of Physiology, 1987