Department of Biological Sciences, 1012 Fairchild, Columbia University, New York, NY 10027,
Sensory signaling by chemicals and light are fairly well understood in molecular terms, but the molecules needed for mechanical signaling, which underlies the senses of touch, hearing, and balance are not known. By analyzing the genes needed for mechanosensation in the nematode Caenorhabditis elegans, we hope to gain this molecular understanding. Six touch receptor neurons respond to gentle touch in C. elegans. Mutations producing touch insensitivity have identified twelve mec (mechanosensory abnormal) genes needed for touch cell function. Nine of these genes have been cloned by ourselves and others. Three genes (mec-4, mec-6, and mec-10) encode similar subunits (degenerins) of a channel needed for mechanosensation. Gene interaction studies suggest that many of the remaining mec genes interact with this channel. Predicted protein sequences, gene interactions, and ultrastructural studies of the touch receptor neurons suggest the following model for mechanosensation in these cells. Mechanosensation requires the degenerin channel formed from MEC-4, MEC-6 and MEC-10. This channel is attached to the extracellular matrix, perhaps through interactions with MEC-5 (a collagen) and possibly MEC-1 and MEC-9. Intracellularly, the channel is attached to the microtubules formed by MEC-12 (alpha-tubulin) and MEC-7 (beta-tubulin), through an interaction with the stomatin-like protein MEC-2. The other mec genes may modifying the conductance of this channel. In this model physical manipulation of the channel either by displacement of the cuticle or the microtubules opens the channel.