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MBC in Press, published online ahead of print February 15, 2006
Mol. Biol. Cell 10.1091/mbc.E05-10-0935

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Submitted on October 11, 2005
Revised on February 2, 2006
Accepted on February 8, 2006

Casein Kinase II and Calcineurin Modulate TRPP Function and Ciliary Localization

Jinghua Hu,*{dagger} Young-Kyung Bae,{dagger}{ddagger} Karla M. Knobel,*{dagger} and Maureen M. Barr*{dagger}

*Division of Pharmaceutical Sciences, {ddagger}Laboratory of Genetics, and {dagger}School of Pharmacy, University of Wisconsin, Madison, WI 53705

Monitoring Editor: Martin Chalfie

Cilia serve as sensory devices in a diversity of organisms and their defects contribute to many human diseases. In primary cilia of kidney cells, the transient receptor potential polycystin (TRPP) channels polycystin-1 (PC-1) and polycystin-2 (PC-2) act as a mechanosensitive channel, with defects resulting in autosomal dominant polycystic kidney disease. In sensory cilia of Caenorhabditis elegans male-specific neurons, the TRPPs LOV-1 and PKD-2 are required for mating behavior. The mechanisms regulating TRPP ciliary localization and function are largely unknown. We identified the regulatory subunit of the serine-theonine casein kinase II (CK2) as a binding partner of LOV-1 and human PC-1. CK2 and the calcineurin phosphatase TAX-6 modulate male mating behavior and PKD-2 ciliary localization. The phospho-defective mutant PKD-2S534A localizes to cilia while a phospho-mimetic PKD-2S534D mutant is largely absent from cilia. Calcineurin is required for PKD-2 ciliary localization, but is not essential for ciliary gene expression, ciliogenesis, or localization of cilium structural components. This unanticipated function of calcineurin may be important for regulating ciliary protein localization. A dynamic phosphorylation-dephosphorylation cycle may represent a mechanism for modulating TRPP activity, cellular sensation, and ciliary protein localization.


Address correspondence to: Maureen M. Barr (mmbarr{at}pharmacy.wisc.edu)




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