Identification of the mechanotransduction channel of cochlear hair cells

• Applicant: Dr. Thomas Friedrich Johannes Wagner
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells
• Term: from 2010 to 2012
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 169840094

Mechanotransduction, the transformation of mechanical force into an electrical signal, allows living organisms to hear, register movement and gravity, detect touch, and sense changes in cell volume and shape. Mechanotransduction depends on transducer channels, which are directly gated by mechanical force. Despite the fundamental importance of mechanotransduction for perception, the molecular identity of vertebrate transducer channels and their accessory proteins are largely not known. The goal of the proposed project is to identify the transduction channel of cochlear hair cells. Using Ca2+ imaging at high resolution, the localization of the hair cell’s transduction channel has recently been defined with high spatial resolution (Beurg et al. 2009). The Mueller laboratory has also identified two ion channels, MTCC1 and MTCC2, which are exclusively found in hair cells at this predicted transduction channel location. I therefore hypothesize that MTCC1 and/or MTCC2 are constituents of the transducer channel. To test this hypothesis, I will determine the extent to which MTCC1 and MTCC2 are required for mechanotransduction by cochlear hair cells and gated by mechanical force. I will analyze hearing function and mechanotransduction in primary hair cells from MTCC1 and MTCC2 knock-out animals and characterize MTCC1 and MTCC2 by electrophysiology in heterologous cells. I anticipate that MTCC1 and/or MTCC2 are gated by mechanical force and essential for auditory perception and possibly other sensory modalities.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Dr. Ulrich Mueller