Interactions between extracellular matrix molecules and the mechanosensory channel complex in Caenorhabditis elegans touch-sensing neurons.

摘要

The touch sensing neurons of C. elegans are attached to the animal's cuticle by structures that span the neighboring epidermal tissue (the hypodermis). In touch-sensing neurons, the localization of the putative mechanosensory channel complexes (MCCs) coincide with the attachment structures in the neighboring hypodermis. At these loci, the touch neurons likely contain a C. elegans focal adhesion-like complex, raising the possibility that mechanosensory transduction in C. elegans is mediated by a focal adhesion-like assembly. Extracellular proteins MEC-1 and collagen MEC-5 associate closely with MCCs at high concentration, and they, along with MEC-9, are required for correct localization of the channel complex. MEC-1 and MEC-5 also appear to coat the touch neuron axon diffusely, though at a lower concentration; however, the presence of MEC-1 and MEC-5 at touch neuron-hypoderma junctions, containing the channel complex, is required for touch sensing whereas their presence between junctions is not. The diffuse coating of MEC-5 and MEC-1 of the touch cell axons, but not the puncta, require ECM protein HIM-4. The intense MEC-5 and MEC-1 puncta on the touch cell axon, but not the diffuse staining, requires MEC-9. MEC-1 is a large extracellular protein with 15 Kunitz domains and 2 EGF domains. The Kunitz domains of MEC-1 do not share important sequence features with vertebrate Kunitz domains that inhibit proteases and are likely to function as protein-protein interaction domains. MEC-1 is required for touch cell attachment and touch sensitivity separately. Two Kunitz domains are suggested to function in binding of MEC-1 to the touch sensing neurons, and two different Kunitz domains are implicated specifically in attaching the neurons to the cuticle. Binding of the MEC-5 collagen to the touch neurons requires the same domains of MEC-1 as does attachment, suggesting that MEC-1 mediates MEC-5 binding indirectly through recruitment of the MEC-5 receptor during attachment; integrin dimer INA-1/PAT-3 is a likely MEC-5 receptor.