Casein kinase II and calcineurin modulate TRPP function and ciliary localization

Jinghua Hu, Young Kyung Bae, Karla M. Knobel, Maureen M. Barr

Research output: Contribution to journalArticle

49 Scopus citations

Abstract

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-2 S534D 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.

Original languageEnglish (US)
Pages (from-to)2200-2211
Number of pages12
JournalMolecular biology of the cell
Volume17
Issue number5
DOIs
StatePublished - May 2006

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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