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MPS-1 is a K+ channel β-subunit and a serine/threonine kinase

Nature Neuroscience volume 8, pages 15031509 (2005) | Download Citation

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Abstract

We report the first example of a K+ channel β-subunit that is also a serine/threonine kinase. MPS-1 is a single–transmembrane domain protein that coassembles with voltage-gated K+ channel KVS-1 in the nervous system of the nematode Caenorhabditis elegans. Biochemical analysis shows that MPS-1 can phosphorylate KVS-1 and other substrates. Electrophysiological analysis in Chinese hamster ovary (CHO) cells demonstrates that MPS-1 activity leads to a significant decrease in the macroscopic current. Single-channel analysis and biotinylation assays indicate that MPS-1 reduces the macroscopic current by lowering the open probability of the channel. These data are consistent with a model that predicts that the MPS-1–dependent phosphorylation of KVS-1 sustains cell excitability by controlling K+ flux.

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Acknowledgements

We thank L. Runnels, A. Ryazanov and J. Lenard for their comments on the manuscript and Fulvio Sesti for help with the graphics. This work was supported by grant R01GM68581-01 from the US National Institutes of Health to F.S.

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  1. University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Department of Physiology and Biophysics, 683 Hoes Lane, Piscataway, New Jersey 08854, USA.

    • Shi-Qing Cai
    • , Leonardo Hernandez
    • , Yi Wang
    • , Ki Ho Park
    •  & Federico Sesti

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The authors declare no competing financial interests.

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Correspondence to Federico Sesti.

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https://doi.org/10.1038/nn1557

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