Publication Date:
2013-12-18
Description:
Primary cilia are solitary, non-motile extensions of the centriole found on nearly all nucleated eukaryotic cells between cell divisions. Only approximately 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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4112737/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4112737/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Delling, Markus -- DeCaen, Paul G -- Doerner, Julia F -- Febvay, Sebastien -- Clapham, David E -- P01 NS072040/NS/NINDS NIH HHS/ -- P30 HD018655/HD/NICHD NIH HHS/ -- P30-HD 18655/HD/NICHD NIH HHS/ -- T32-HL007572/HL/NHLBI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2013 Dec 12;504(7479):311-4. doi: 10.1038/nature12833.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Howard Hughes Medical Institute, Department of Cardiology, Boston Children's Hospital, 320 Longwood Avenue, Boston, Massachusetts 02115, USA [2]. ; Howard Hughes Medical Institute, Department of Cardiology, Boston Children's Hospital, 320 Longwood Avenue, Boston, Massachusetts 02115, USA. ; 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.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24336288" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Calcium/metabolism
;
Calcium Channels/chemistry/*metabolism
;
*Calcium Signaling
;
Cells, Cultured
;
Cilia/*metabolism
;
Cytoplasm/metabolism
;
Female
;
Hedgehog Proteins/deficiency/genetics/*metabolism
;
Humans
;
Kruppel-Like Transcription Factors/metabolism
;
Male
;
Membrane Proteins/chemistry/deficiency/metabolism
;
Mice
;
Nuclear Proteins/metabolism
;
Organelles/*metabolism
;
Receptors, Cell Surface/chemistry/metabolism
;
Receptors, G-Protein-Coupled/metabolism
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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