Casein kinase II and calcineurin modulate TRPP function and ciliary localization.
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-2(S534A) 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.
Division of Pharmaceutical Sciences, University of Wisconsin, Madison, WI 53705, USA.
Jinghua
J
Hu
Young-Kyung
YK
Bae
Karla M
KM
Knobel
Maureen M
MM
Barr
D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000033:anatomy & histology / Q000737:chemistry / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000032:analysis / Q000378:metabolism*; D019703:Calcineurin / Q000378:metabolism*; D047390:Casein Kinase II / Q000378:metabolism*; D002923:Cilia / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D025941:Protein Interaction Mapping; D012726:Sexual Behavior, Animal; D050396:TRPP Cation Channels / Q000032:analysis / Q000378:metabolism*
D029742:Caenorhabditis elegans Proteins; D019703:Calcineurin; D047390:Casein Kinase II; D010744:Phosphoric Monoester Hydrolases; D050396:TRPP Cation Channels; C120817:calcineurin phosphatase