Research ArticleNeuroscience

Peripheral motor neuropathy is associated with defective kinase regulation of the KCC3 cotransporter

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Science Signaling  02 Aug 2016:
Vol. 9, Issue 439, pp. ra77
DOI: 10.1126/scisignal.aae0546

Neuropathic KCC3 activity

Clinical presentation of disease by patients can lead to profoundly important discoveries about basic biology. In this case, a child with progressive, early-onset, motor neuropathy resulting in profound disability revealed a key role for the phosphorylation-mediated regulation of the K+-Cl transporter KCC3 in the peripheral nervous system. Kahle et al. discovered a point mutation in the gene encoding KCC3 in the patient that prevented the transporter from being inhibited through phosphorylation and resulted in its constitutive activation. Mice expressing KCC3 with the same mutation had increased transporter activity and impaired locomotor function, suggesting that the normal function of peripheral neurons depends on the regulation of KCC3 function.

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