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Originally published as MBC in Press, 10.1091/mbc.E05-10-0935 on February 15, 2006

Vol. 17, Issue 5, 2200-2211, May 2006

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Casein Kinase II and Calcineurin Modulate TRPP Function and Ciliary LocalizationFormula

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

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

Submitted October 11, 2005; Revised February 2, 2006; Accepted February 8, 2006
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-threonine 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, whereas 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.

This article was published online ahead of print in MBC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E05–10–0935) on February 15, 2006.

Formula The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).

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




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