西亚试剂：Direct recording and molecular identification of the calciu

发布时间：2025-12-18

Direct recording and molecular identification of the calcium channel of primary cilia

Paul G. DeCaen，Markus Delling，Thuy N. Vien& David E. Clapham

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， primary cilia also serve as specialized compartments for calcium signalling2 and hedgehog signalling pathways3. Specialized sensory cilia such as retinal photoreceptors and olfactory cilia use diverse ion channels4， 5， 6， 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 and PKD)， identified in linkage studies of polycystic kidney disease9， are candidate channels divided into two structural classes： 11-transmembrane proteins (PKD1， PKD1L1 and PKD1L2) remarkable for a large extracellular amino terminus of putative cell adhesion domains and a G-protein-coupled receptor proteolytic site， and the 6-transmembrane channel proteins (PKD2， PKD2L1 and PKD2L2； TRPPs). Evidence indicates that the PKD1 proteins associate with the PKD2 proteins via coiled-coil domains10， 11， 12. Here we use a transgenic mouse in which only cilia express a fluorophore and use it to record directly from primary cilia， and demonstrate that PKD1L1 and PKD2L1 form ion channels at high densities in several cell types. In conjunction with an accompanying manuscript2， we show that the PKD1L1–PKD2L1 heteromeric channel establishes the cilia as a unique calcium compartment within cells that modulates established hedgehog pathways.

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