title: Primary cilia are specialized calcium signalling organelles.
abstract: Primary cilia are solitary, non-motile extensions of the centriole found on nearly all nucleated eukaryotic cells between cell divisions. Only ∼200-300 nm in diameter and a few micrometres long, they are separated from the cytoplasm by the ciliary neck and basal body. Often called sensory cilia, they are thought to receive chemical and mechanical stimuli and initiate specific cellular signal transduction pathways. When activated by a ligand, hedgehog pathway proteins, such as GLI2 and smoothened (SMO), translocate from the cell into the cilium. Mutations in primary ciliary proteins are associated with severe developmental defects. The ionic conditions, permeability of the primary cilia membrane, and effectiveness of the diffusion barriers between the cilia and cell body are unknown. Here we show that cilia are a unique calcium compartment regulated by a heteromeric TRP channel, PKD1L1-PKD2L1, in mice and humans. In contrast to the hypothesis that polycystin (PKD) channels initiate changes in ciliary calcium that are conducted into the cytoplasm, we show that changes in ciliary calcium concentration occur without substantially altering global cytoplasmic calcium. PKD1L1-PKD2L1 acts as a ciliary calcium channel controlling ciliary calcium concentration and thereby modifying SMO-activated GLI2 translocation and GLI1 expression.
authors: 1] Howard Hughes Medical Institute, Department of Cardiology, Boston Children's Hospital, 320 Longwood Avenue, Boston, Massachusetts 02115, USA [2].
authors: Markus
authors: M
authors: Delling
authors: 1] Howard Hughes Medical Institute, Department of Cardiology, Boston Children's Hospital, 320 Longwood Avenue, Boston, Massachusetts 02115, USA [2].
authors: Paul G
authors: PG
authors: DeCaen
authors: Howard Hughes Medical Institute, Department of Cardiology, Boston Children's Hospital, 320 Longwood Avenue, Boston, Massachusetts 02115, USA.
authors: Julia F
authors: JF
authors: Doerner
authors: Howard Hughes Medical Institute, Department of Cardiology, Boston Children's Hospital, 320 Longwood Avenue, Boston, Massachusetts 02115, USA.
authors: Sebastien
authors: S
authors: Febvay
authors: 1] Howard Hughes Medical Institute, Department of Cardiology, Boston Children's Hospital, 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; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000737:chemistry / Q000378:metabolism*; D020013:Calcium Signaling; D002478:Cells, Cultured; D002923:Cilia / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D005260:Female; D053823:Hedgehog Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000737:chemistry / Q000172:deficiency / Q000378:metabolism; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism; D015388:Organelles / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D000072086:Smoothened Receptor; D000071676:Zinc Finger Protein GLI1; D000075746:Zinc Finger Protein Gli2
chemical_list: D015220:Calcium Channels; C082593:GLI2 protein, human; C498520:Gli1 protein, mouse; D053823:Hedgehog Proteins; D051741:Kruppel-Like Transcription Factors; D008565:Membrane Proteins; D009687:Nuclear Proteins; C455507:PKD1L1 protein, human; C117185:PKD2L1 protein, human; C486742:Pkd1l1 protein, mouse; C486487:Pkd2l1 protein, mouse; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C465570:Shh protein, mouse; C491022:Smo protein, mouse; D000072086:Smoothened Receptor; D000071676:Zinc Finger Protein GLI1; D000075746:Zinc Finger Protein Gli2; D002118:Calcium