Mode of action of the Gαi/Gpsm2 and the RGS4/neurabin complex in cochlear hair cells
Bernd Nürnberg & Ellen Reisinger
During the development of the inner ear, Gαi3 and its non-canonical regulator Gpsm2 play an essential role for orienting sensory hair cells. GPSM2 mutations cause profound early-onset sensorineural hearing impairment in human patients that are mimicked in mutant mouse models. Very recently, an orphan GPCR of unknown function was identified to activate Gαi3, thereby triggering hair cell orientation. An additional interaction of Gαi3 with the guanine nucleotide exchange modulator Daple has been reported. Our goal is to decipher the molecular players and the interplay of their signaling to understand how the correct orientation of sensory cells of the inner ear epithelium is achieved. In this project we aim to unravel upstream regulators and downstream effectors of Gpsm2/Gαi during hair cell development, and the differential functions of Gαi2 and Gαi3 in apical (low frequency) vs. basal (high frequency sensing) hair cells.