کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2177895 1094692 2006 13 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Polycystin-1, STAT6, and P100 Function in a Pathway that Transduces Ciliary Mechanosensation and Is Activated in Polycystic Kidney Disease
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
پیش نمایش صفحه اول مقاله
Polycystin-1, STAT6, and P100 Function in a Pathway that Transduces Ciliary Mechanosensation and Is Activated in Polycystic Kidney Disease
چکیده انگلیسی

SummaryPrimary cilia are implicated in the pathogenesis of autosomal-dominant polycystic kidney disease (ADPKD), which results from defects in polycystin-1 (PC1), but the function of PC1 remains poorly understood. Here, we show that PC1 undergoes proteolytic cleavage that results in nuclear translocation of its cytoplasmic tail. The PC1 tail interacts with the transcription factor STAT6 and the coactivator P100, and it stimulates STAT6-dependent gene expression. Under normal conditions, STAT6 localizes to primary cilia of renal epithelial cells. Cessation of apical fluid flow results in nuclear translocation of STAT6. Cyst-lining cells in ADPKD exhibit elevated levels of nuclear STAT6, P100, and the PC1 tail. Exogenous expression of the human PC1 tail results in renal cyst formation in zebrafish embryos. These results identify a novel mechanism of cilia function in the transduction of a mechanical signal to changes of gene expression involving PC1 and show that this pathway is inappropriately activated in ADPKD.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: - Volume 10, Issue 1, January 2006, Pages 57–69
نویسندگان
, , , , , , , , ,