Document Detail


Polycystin-1 and -2 dosage regulates pressure sensing.
MedLine Citation:
PMID:  19879844     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Autosomal-dominant polycystic kidney disease, the most frequent monogenic cause of kidney failure, is induced by mutations in the PKD1 or PKD2 genes, encoding polycystins TRPP1 and TRPP2, respectively. Polycystins are proposed to form a flow-sensitive ion channel complex in the primary cilium of both epithelial and endothelial cells. However, how polycystins contribute to cellular mechanosensitivity remains obscure. Here, we show that TRPP2 inhibits stretch-activated ion channels (SACs). This specific effect is reversed by coexpression with TRPP1, indicating that the TRPP1/TRPP2 ratio regulates pressure sensing. Moreover, deletion of TRPP1 in smooth muscle cells reduces SAC activity and the arterial myogenic tone. Inversely, depletion of TRPP2 in TRPP1-deficient arteries rescues both SAC opening and the myogenic response. Finally, we show that TRPP2 interacts with filamin A and demonstrate that this actin crosslinking protein is critical for SAC regulation. This work uncovers a role for polycystins in regulating pressure sensing.
Authors:
Reza Sharif-Naeini; Joost H A Folgering; Delphine Bichet; Fabrice Duprat; Inger Lauritzen; Malika Arhatte; Martine Jodar; Alexandra Dedman; Franck C Chatelain; Uwe Schulte; Kevin Retailleau; Laurent Loufrani; Amanda Patel; Frederick Sachs; Patrick Delmas; Dorien J M Peters; Eric Honoré
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cell     Volume:  139     ISSN:  1097-4172     ISO Abbreviation:  Cell     Publication Date:  2009 Oct 
Date Detail:
Created Date:  2009-11-02     Completed Date:  2009-12-03     Revised Date:  2009-12-31    
Medline Journal Info:
Nlm Unique ID:  0413066     Medline TA:  Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  587-96     Citation Subset:  IM    
Affiliation:
Institut de Pharmacologie Moléculaire et Cellulaire, UMR CNRS 6097, Université de Nice Sophia Antipolis, 06560 Valbonne, France.
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MeSH Terms
Descriptor/Qualifier:
Actins / metabolism
Animals
Contractile Proteins / metabolism
Mechanotransduction, Cellular
Mice
Microfilament Proteins / metabolism
Muscle, Smooth, Vascular / metabolism
Myocytes, Smooth Muscle / metabolism
Pressoreceptors / metabolism
Pressure*
TRPP Cation Channels / metabolism*
Chemical
Reg. No./Substance:
0/Actins; 0/Contractile Proteins; 0/Microfilament Proteins; 0/TRPP Cation Channels; 0/filamins; 0/polycystic kidney disease 1 protein; 0/polycystic kidney disease 2 protein
Comments/Corrections
Comment In:
Kidney Int. 2010 Jan;77(2):81   [PMID:  20040919 ]
Cell. 2009 Oct 30;139(3):466-7   [PMID:  19879836 ]

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