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http://purl.uniprot.org/citations/25888683http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/25888683http://www.w3.org/2000/01/rdf-schema#comment"

Background

L-type calcium channel activity is critical to afterload-induced hypertrophic growth of the heart. However, the mechanisms governing mechanical stress-induced activation of L-type calcium channel activity are obscure. Polycystin-1 (PC-1) is a G protein-coupled receptor-like protein that functions as a mechanosensor in a variety of cell types and is present in cardiomyocytes.

Methods and results

We subjected neonatal rat ventricular myocytes to mechanical stretch by exposing them to hypo-osmotic medium or cyclic mechanical stretch, triggering cell growth in a manner dependent on L-type calcium channel activity. RNAi-dependent knockdown of PC-1 blocked this hypertrophy. Overexpression of a C-terminal fragment of PC-1 was sufficient to trigger neonatal rat ventricular myocyte hypertrophy. Exposing neonatal rat ventricular myocytes to hypo-osmotic medium resulted in an increase in α1C protein levels, a response that was prevented by PC-1 knockdown. MG132, a proteasomal inhibitor, rescued PC-1 knockdown-dependent declines in α1C protein. To test this in vivo, we engineered mice harboring conditional silencing of PC-1 selectively in cardiomyocytes (PC-1 knockout) and subjected them to mechanical stress in vivo (transverse aortic constriction). At baseline, PC-1 knockout mice manifested decreased cardiac function relative to littermate controls, and α1C L-type calcium channel protein levels were significantly lower in PC-1 knockout hearts. Whereas control mice manifested robust transverse aortic constriction-induced increases in cardiac mass, PC-1 knockout mice showed no significant growth. Likewise, transverse aortic constriction-elicited increases in hypertrophic markers and interstitial fibrosis were blunted in the knockout animals

Conclusion

PC-1 is a cardiomyocyte mechanosensor that is required for cardiac hypertrophy through a mechanism that involves stabilization of α1C protein."xsd:string
http://purl.uniprot.org/citations/25888683http://purl.org/dc/terms/identifier"doi:10.1161/circulationaha.114.013537"xsd:string
http://purl.uniprot.org/citations/25888683http://purl.uniprot.org/core/author"Fernandez C."xsd:string
http://purl.uniprot.org/citations/25888683http://purl.uniprot.org/core/author"Jiang N."xsd:string
http://purl.uniprot.org/citations/25888683http://purl.uniprot.org/core/author"Luo X."xsd:string
http://purl.uniprot.org/citations/25888683http://purl.uniprot.org/core/author"Hill J.A."xsd:string
http://purl.uniprot.org/citations/25888683http://purl.uniprot.org/core/author"Morales C.R."xsd:string
http://purl.uniprot.org/citations/25888683http://purl.uniprot.org/core/author"Caplan M.J."xsd:string
http://purl.uniprot.org/citations/25888683http://purl.uniprot.org/core/author"Somlo S."xsd:string
http://purl.uniprot.org/citations/25888683http://purl.uniprot.org/core/author"Criollo A."xsd:string
http://purl.uniprot.org/citations/25888683http://purl.uniprot.org/core/author"Rothermel B.A."xsd:string
http://purl.uniprot.org/citations/25888683http://purl.uniprot.org/core/author"Gillette T.G."xsd:string
http://purl.uniprot.org/citations/25888683http://purl.uniprot.org/core/author"Lavandero S."xsd:string
http://purl.uniprot.org/citations/25888683http://purl.uniprot.org/core/author"Battiprolu P.K."xsd:string
http://purl.uniprot.org/citations/25888683http://purl.uniprot.org/core/author"Contreras-Ferrat A."xsd:string
http://purl.uniprot.org/citations/25888683http://purl.uniprot.org/core/author"Pedrozo Z."xsd:string
http://purl.uniprot.org/citations/25888683http://purl.uniprot.org/core/date"2015"xsd:gYear
http://purl.uniprot.org/citations/25888683http://purl.uniprot.org/core/name"Circulation"xsd:string
http://purl.uniprot.org/citations/25888683http://purl.uniprot.org/core/pages"2131-2142"xsd:string
http://purl.uniprot.org/citations/25888683http://purl.uniprot.org/core/title"Polycystin-1 Is a Cardiomyocyte Mechanosensor That Governs L-Type Ca2+ Channel Protein Stability."xsd:string
http://purl.uniprot.org/citations/25888683http://purl.uniprot.org/core/volume"131"xsd:string
http://purl.uniprot.org/citations/25888683http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/25888683
http://purl.uniprot.org/citations/25888683http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/25888683
http://purl.uniprot.org/uniprot/#_A0A087WPP1-mappedCitation-25888683http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/25888683
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