Direct recording and molecular identification of the calcium channel of primary cilia
DeCaen, Paul G.
Vien, Thuy N.
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CitationDeCaen, Paul G., Markus Delling, Thuy N. Vien, and David E. Clapham. 2014. “Direct recording and molecular identification of the calcium channel of primary cilia.” Nature 504 (7479): 315-318. doi:10.1038/nature12832. http://dx.doi.org/10.1038/nature12832.
AbstractSummary A primary cilium is a solitary slender non-motile protuberance of structured microtubules (9+0) enclosed by plasma membrane1. Housing components of the cell division apparatus between cell divisions, they also serve as specialized compartments for calcium signaling2 and Hedgehog (Hh) signaling pathways3. Specialized sensory cilia such as retinal photoreceptors and olfactory cilia employ diverse ion channels4-7. An ion current has been measured from primary cilia of kidney cells8 but the responsible genes have not been identified. The polycystin proteins (PC, PKD), identified in linkage studies of polycystic kidney disease9, are candidate channels divided into two structural classes: 11-transmembrane (TM) proteins (PKD1, PKD1-L1 and PKD1-L2) remarkable for a large extracellular N-terminus of putative cell adhesion domains and a GPCR proteolytic site, and the 6-TM channel proteins (PKD2, PKD2-L1, PKD2-L2; TRPPs). Evidence suggests that the PKD1s associate with the PKD2s via coiled-coil domains10-12. Here, we employ a transgenic mouse in which only cilia express a fluorophore and employ it to directly record from primary cilia and demonstrate that PKD1-L1 and PKD2-L1 form ion channels at high densities in several cell types. In conjunction with the companion manuscript2, we show that the PKD1-L1/PKD2-L1 heteromeric channel establishes the cilia as a unique calcium compartment within cells that modulates established Hedgehog pathways.
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