Molekulare Grundlagen der Mechanotransduktion bei sensorischen Neuronen

• Applicant: Professor Gary Richard Lewin, Ph.D.
• Subject Area: Biochemistry
• Term: from 1999 to 2004
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5171642

The molecular basis of sensory neuron mechanotransduction is unknown. We study the expression of mammalian genes related to C.elegans mec genes found in a genetic screen for touch insensitive mutants. We have used an in vitro electrophysiological assay to record from single sensory neurons innervating skin in genetically modified mice. Recently, we have examined stomatin knockout mice, stomatin has high sequence homology to the C.elegans mec-2 gene. We have shown that stomatin is expressed by sensory neurons of the dorsal root ganglia and data from our physiological studies indicate that sensory mechanotransduction is substantially impaired in stomatin -/- mice. We hypothesize that stomatin links a deg-related ion channel to the cytoskeleton and in this way confers mechanosensitivity on the channel. We have recently cloned a new stomatin-like gene which we term Neural stomatin (Nstomatin). One major aim of the current application is to use molecular genetics (transgenic and knockout) to ask whether this stomatin-related gene also plays a role in mechanotransduction. In addition we will carry out biochemical experiments to isolate a GPI-anchored extracellular protein which appears to be necessary for normal mechanotransduction in sensory neurons.

• DFG Programme: Priority Programmes
• Subproject of: SPP 1025: Molekulare Sinnesphysiologie