Document Detail

Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells.
MedLine Citation:
PMID:  12514735     Owner:  NLM     Status:  MEDLINE    
Several proteins implicated in the pathogenesis of polycystic kidney disease (PKD) localize to cilia. Furthermore, cilia are malformed in mice with PKD with mutations in TgN737Rpw (encoding polaris). It is not known, however, whether ciliary dysfunction occurs or is relevant to cyst formation in PKD. Here, we show that polycystin-1 (PC1) and polycystin-2 (PC2), proteins respectively encoded by Pkd1 and Pkd2, mouse orthologs of genes mutated in human autosomal dominant PKD, co-distribute in the primary cilia of kidney epithelium. Cells isolated from transgenic mice that lack functional PC1 formed cilia but did not increase Ca(2+) influx in response to physiological fluid flow. Blocking antibodies directed against PC2 similarly abolished the flow response in wild-type cells as did inhibitors of the ryanodine receptor, whereas inhibitors of G-proteins, phospholipase C and InsP(3) receptors had no effect. These data suggest that PC1 and PC2 contribute to fluid-flow sensation by the primary cilium in renal epithelium and that they both function in the same mechanotransduction pathway. Loss or dysfunction of PC1 or PC2 may therefore lead to PKD owing to the inability of cells to sense mechanical cues that normally regulate tissue morphogenesis.
Surya M Nauli; Francis J Alenghat; Ying Luo; Eric Williams; Peter Vassilev; Xiaogang Li; Andrew E H Elia; Weining Lu; Edward M Brown; Stephen J Quinn; Donald E Ingber; Jing Zhou
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.     Date:  2003-01-06
Journal Detail:
Title:  Nature genetics     Volume:  33     ISSN:  1061-4036     ISO Abbreviation:  Nat. Genet.     Publication Date:  2003 Feb 
Date Detail:
Created Date:  2003-01-31     Completed Date:  2003-03-04     Revised Date:  2007-10-18    
Medline Journal Info:
Nlm Unique ID:  9216904     Medline TA:  Nat Genet     Country:  United States    
Other Details:
Languages:  eng     Pagination:  129-37     Citation Subset:  IM; S    
Renal Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 4 Blackfan Circle, Boston, Massachusetts 02115, USA.
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MeSH Terms
Caffeine / pharmacology
Calcium / metabolism*
Calcium Channels / physiology
Cilia / physiology*
Epithelium / metabolism*
GTP-Binding Proteins / metabolism
Homeostasis / physiology*
Kidney / metabolism
Membrane Proteins / physiology*
Mice, Knockout
Polycystic Kidney, Autosomal Dominant / physiopathology*
Protein Binding
Protein Transport
Proteins / physiology*
Ryanodine Receptor Calcium Release Channel / metabolism
Signal Transduction / physiology
TRPP Cation Channels
Tubulin / metabolism
Reg. No./Substance:
0/Calcium Channels; 0/Membrane Proteins; 0/Proteins; 0/Ryanodine Receptor Calcium Release Channel; 0/TRPP Cation Channels; 0/Tubulin; 0/polycystic kidney disease 1 protein; 0/polycystic kidney disease 2 protein; 58-08-2/Caffeine; 7440-70-2/Calcium; EC 3.6.1.-/GTP-Binding Proteins
D E Ingber / Harvard Med Sch, Boston, MA
Comment In:
Nat Genet. 2003 Feb;33(2):113-4   [PMID:  12514736 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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