Die Funktion von Melanopsin in mechanosensorischen Neuronen

What was previously known? Hair cells, the primary receptors of auditory and lateral line sensory systems, are neuroepithelial cells with protruding bundles of stereocilia that are deflected by pressure. Displacement of these stereocilia stretches linkages at their tips, thereby gating mechanotransduction channels and inducing electrical currents. The molecular details underlying this transduction process are only partially understood. A recent Drosophila screen for auditory organ genes revealed mechanical amplification by Johnstons neurons to be severely impaired by mutations in rhodopsin, demonstrating its requirement for mechanotransduction. Rhodopsin is a pigment in the photoreceptor cells of the fruit flys retina that is responsible for the first step in the perception of light. We discovered two melanopsins, photoreceptors known for their function in photosensitive retinal ganglion cells, to be expressed in the mechanosensory hair cells of the zebrafish lateral line. The expression of orthologous opsins in invertebrate and vertebrate mechanosensory cells strongly implies that zebrafish melanopsin plays a role in vertebrate mechanosensation. What is the conceptual advance? The direct use of the force provided by a mechanical stimulus in opening a transducer channel is considered to be the hallmark of the mechanical senses. In contrast, light cannot exert pressure and thus the light sensory system is thought to rely on indirect second messenger dependent transducers. Recently, however Drosophila rhodopsin has been shown to induce a mechanical force on the cell membrane upon activation. To date photoreceptors have not been implied in vertebrate mechanosensation or its modulation. I aim to reveal the role of melanopsins in zebrafish hair cells, and have for this purpose generated mutants by reverse genetics. Melanopsin could either have a direct role in mechanotransduction, which is light independent, or modulate the mechanosensory signal in a light dependent manner. These hypotheses will be tested by analysis of the melanopsin mutant on the molecular, electrophysiological and behavioural levels. What is the significance of this study for the advancement of science? 1) This study breaks down the molecular and conceptual boundaries between the mechanical and non- mechanical senses. 2) This study will lead to a conceptual advance in our understanding of vertebrate mechanosensation, which is so far not associated with a light receptive molecule. 3) This study will provide substantial new mechanistic insight into the function of melanopsins.