Quantification of lateral associations of achondroplasia in FGFR3.

Abstract

Fibroblast growth factor receptor 3 (FGFR3) belongs to the receptor tyrosine kinase (RTK) family and is a key player in bone growth, tumor angiogenesis, and other developmental processes. Of particular interest is a substitution of glycine to arginine (G380R) in the transmembrane domain, which is implicated in human achondroplasia. The G380R mutation has been reported to stabilize FGFR3 dimers in the absence of ligand; however, recent work has suggested that the G380R mutation may be inducing the formation of FGFR3 oligomers that are larger than dimers. This has propelled us to re-evaluate the effect of the mutation on FGFR3 self-association in the plasma membrane of live cells using a quantitative fluorescence method, FSI-FRET, which reports on oligomer size, stability, and structure. This project aims to re-examine the self-association of both wild type and G380R mutant FGFR3 over physiologically relevant receptor concentrations and under different growth factor conditions using FSI-FRET.