Protein kinase WNK3 regulates the neuronal splicing factor Fox-1.

Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390.
Proceedings of the National Academy of Sciences (Impact Factor: 9.81). 10/2012; 109(42):16841-6. DOI: 10.1073/pnas.1215406109
Source: PubMed

ABSTRACT We report an action of the protein kinase WNK3 on the neuronal mRNA splicing factor Fox-1. Fox-1 splices mRNAs encoding proteins important in synaptic transmission and membrane excitation. WNK3, implicated in the control of neuronal excitability through actions on ion transport, binds Fox-1 and inhibits its splicing activity in a kinase activity-dependent manner. Phosphorylation of Fox-1 by WNK3 does not change its RNA binding capacity; instead, WNK3 increases the cytoplasmic localization of Fox-1, thereby suppressing Fox-1-dependent splicing. These findings demonstrate a role of WNK3 in RNA processing. Considering the implication of WNK3 and Fox-1 in disorders of neuronal development such as autism, WNK3 may offer a target for treatment of Fox-1-induced disease.

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