Characterization of TRPC6 mutations in inherited FSGS

Brigham And Women'S Hospital, Boston MA

Investigators

Linked publications & trials

Abstract

[unreadable] DESCRIPTION (provided by applicant): Focal segmental glomerular sclerosis (FSGS) is a kidney lesion seen in a number of disease states, and contributes significantly to the population of patients with end-stage renal disease. Several inherited forms of FSGS have been described. Mutations identified to date involve proteins expressed in the podocyte, and studies of inherited FSGS have furthered our understanding of how podocytes help maintain the filtration barrier that prevents protein from spilling into the urine. Recently, mutations in TRPC6, a calcium channel, have been identified as causing an autosomal dominant form of FSGS. Mutations have been found to involve several different areas of the TRPC6 protein, yet how they might affect TRPC6 function is unclear. We propose several lines of investigation to characterize these mutations in cell based and in vitro systems, including possible effects on protein stability, localization, phosphorylation, and channel activity. In addition, we plan to assess the ability of these mutant channels to multimerize with other TRPC family members as well as bind to key components of the podocyte slit diaphragm. These studies will further open new lines of investigation into how TRPC6 function is crucial for proper podocyte function. [unreadable] [unreadable]