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

Nature Neuroscience volume 8, pages 1503–1509 (2005)Cite this article

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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Figure 1: MPS-1 shows characteristic protein kinase motifs.
Figure 2: MPS-1 phosphorylates MBP in vitro.
Figure 3: MPS-1 activity can be detected by antibodies to phosphoserine and phosphothreonine (anti-pS/pT).
Figure 4: MPS-1 phosphorylates KVS-1 in CHO cells.
Figure 5: MPS-1 kinase activity decreases the macroscopic current.
Figure 6: MPS-1 decreases the open probability of the KVS-1 channel.
Figure 7: Fluctuation analysis of KVS-1 and KVS-1–MPS-1 channels.

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

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

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Correspondence to Federico Sesti.

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Cai, SQ., Hernandez, L., Wang, Y. et al. MPS-1 is a K+ channel β-subunit and a serine/threonine kinase. Nat Neurosci 8, 1503–1509 (2005). https://doi.org/10.1038/nn1557

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