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Fragile X mental retardation protein controls gating of the sodium-activated potassium channel Slack

Abstract

In humans, the absence of Fragile X mental retardation protein (FMRP), an RNA-binding protein, results in Fragile X syndrome, the most common inherited form of intellectual disability. Using biochemical and electrophysiological studies, we found that FMRP binds to the C terminus of the Slack sodium-activated potassium channel to activate the channel in mice. Our findings suggest that Slack activity provides a link between patterns of neuronal firing and changes in protein translation.

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Figure 1: FMRP directly binds to Slack channel subunits.
Figure 2: FMRP alters gating of full-length Slack-B channels, but not Slack-BΔ804, in inside-out patches.
Figure 3: IK(Na)-containing component of current is reduced in Fmr1–/y MNTB neurons.

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Acknowledgements

This research was supported by US National Institutes of Health grants NS61479 (M.R.B.), DC008449 (J.K.), DC01919 and the FRAXA Research Foundation (L.K.K.).

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Contributions

M.R.B., J.K. and L.K.K. designed the experiments and wrote the manuscript. M.R.B., J.K., V.-R.G., Y.C., J.G.S. and D.N. performed the experiments. F.J.S. contributed HEK channel cell lines. All of the authors discussed the results and reviewed the manuscript.

Corresponding author

Correspondence to Leonard K Kaczmarek.

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The authors declare no competing financial interests.

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Supplementary Figures 1 and 2, and Supplementary Methods (PDF 141 kb)

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Brown, M., Kronengold, J., Gazula, VR. et al. Fragile X mental retardation protein controls gating of the sodium-activated potassium channel Slack. Nat Neurosci 13, 819–821 (2010). https://doi.org/10.1038/nn.2563

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