title: Direct recording and molecular identification of the calcium channel of primary cilia.
abstract: A primary cilium is a solitary, slender, non-motile protuberance of structured microtubules (9+0) enclosed by plasma membrane. Housing components of the cell division apparatus between cell divisions, primary cilia also serve as specialized compartments for calcium signalling and hedgehog signalling pathways. Specialized sensory cilia such as retinal photoreceptors and olfactory cilia use diverse ion channels. An ion current has been measured from primary cilia of kidney cells, but the responsible genes have not been identified. The polycystin proteins (PC and PKD), identified in linkage studies of polycystic kidney disease, 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 domains. 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 manuscript, we show that the PKD1L1-PKD2L1 heteromeric channel establishes the cilia as a unique calcium compartment within cells that modulates established hedgehog pathways.
authors: 1] Howard Hughes Medical Institute, Department of Cardiology, Children's Hospital Boston, 320 Longwood Avenue, Boston, Massachusetts 02115, USA [2].
authors: Paul G
authors: PG
authors: DeCaen
authors: 1] Howard Hughes Medical Institute, Department of Cardiology, Children's Hospital Boston, 320 Longwood Avenue, Boston, Massachusetts 02115, USA [2].
authors: Markus
authors: M
authors: Delling
authors: Department of Neuroscience, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, Massachusetts 02111, USA.
authors: Thuy N
authors: TN
authors: Vien
authors: 1] Howard Hughes Medical Institute, Department of Cardiology, Children's Hospital Boston, 320 Longwood Avenue, Boston, Massachusetts 02115, USA [2] Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors: David E
authors: DE
authors: Clapham
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D002455:Cell Division; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D002923:Cilia / Q000378:metabolism*; D057809:HEK293 Cells; D053823:Hedgehog Proteins / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D015513:Oncogene Proteins / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D000072086:Smoothened Receptor; D015534:Trans-Activators / Q000378:metabolism; D000071676:Zinc Finger Protein GLI1
chemical_list: D015220:Calcium Channels; D053823:Hedgehog Proteins; D008565:Membrane Proteins; D015513:Oncogene Proteins; C455507:PKD1L1 protein, human; C117185:PKD2L1 protein, human; C486487:Pkd2l1 protein, mouse; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C491023:SMO protein, human; D000072086:Smoothened Receptor; D015534:Trans-Activators; D000071676:Zinc Finger Protein GLI1