Analysis of the polycystins in aortic vascular smooth muscle cells

Qi Qian, Ming Li, Yiqiang Cai, Christopher J. Ward, Stefan Somlo, Peter C. Harris, Vicente E. Torres

Research output: Contribution to journalArticle

68 Scopus citations

Abstract

The leading cause of death in autosomal dominant polycystic kidney disease (ADPKD) is cardiovascular. However, little is known about the pathogenesis of these manifestations. The present study was undertaken to characterize the ADPKD proteins, the polycystins, in vascular smooth muscle cells. It was demonstrated that the expression of polycystin-1 is developmentally regulated, whereas polycystin-2 has a more constant level of expression. A polycystin-1 subpopulation was immunoprecipitated by polycystin-2, indicating an in vivo interaction of these two proteins. Analysis with glycosidase and cell surface biotinylation indicates that some polycystin-1 products, but not polycystin-2, are located on the plasma membrane. Immunofluorescence showed that most of the polycystin-1 and polycystin-2 was cytoplasmic but that persistent polycystin-1 staining was located in proximity to the cell surface after a Triton-X extraction, whereas no clear surface localization of polycystin-2 was detected. Immuno-gold electron microscopy revealed that polycystin-1 was localized at the plasma membrane and sarcoplasmic reticulum, whereas polycystin-2 was mainly located in the sarcoplasmic reticulum. Both polycystins were found to be associated with dense plaques. These observations are consistent with an important role of the polycystins in the development, maintenance, and function of the myoelastic arterial organization and with the vascular phenotype associated with ADPKD.

Original languageEnglish (US)
Pages (from-to)2280-2287
Number of pages8
JournalJournal of the American Society of Nephrology
Volume14
Issue number9
DOIs
StatePublished - Sep 1 2003

ASJC Scopus subject areas

  • Nephrology

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