Food texture, which includes hardness, softness and viscosity, plays an indispensible role in controlling an animal?s taste preference. The texture of food is primarily detected through mechanosensory receptors located in taste organs. Although food texture has enormous impact on food intake behavior, the molecular and cellular identities of mechanosensory receptors responsible for food texture sensation are largely unknown. Transmembrane channel-like (TMC) proteins are highly conserved from worms to flies, mice and humans, and are proposed to be cation channels. However, definitive evidence is lacking. A common theme is that TMC proteins appear to mediate different forms of mechanosensation. For instance, both dominant and recessive mutations affecting TMC1 result in severe hearing impairments in mice and humans. Moreover, our preliminary data suggest that fly TMC is a mechanosensor, which is critical for discriminating foods on the basis of texture. Here, I propose to use the fruit fly as a model organism to dissect the molecular and cellular mechanisms through which mechanical properties of food affect taste preferences. Firstly, I will explore how mechanical force is encoded by tmc-expressing neurons in the peripheral taste organ of fruit fly. Secondly, I will test if the tmc expressing cell is sufficient to act as a mechanosensory neuron. Thirdly, I propose to determine the membrane trafficking and force gating mechanisms of TMC ion channels. In summary, this proposal will test the hypothesis that fly TMC is a mechanosensor dictating food texture sensation, and that TMC defines previously unknown mechanosensory neurons required for detecting food texture in fruit flies.
Dysfunction of TMC1 results in severe hearing impairments in humans, and according to one model, is the long sought-after force sensitive channel in auditory hair cells. Since there is remarkable conservation between fly TMC and human TMC1 in terms of amino acids sequence homology and roles in mechanosensation, the characterization of fly TMC has the potential to provide key insights into the biophysical properties of the human TMC1, and the mechanism through which these putative channels contribute to mechanosensaiton, including the human auditory response.
| Zhang, Yali V; Aikin, Timothy J; Li, Zhengzheng et al. (2016) The Basis of Food Texture Sensation in Drosophila. Neuron 91:863-877 |
