Mechanosensory neurons innervate the skin of nematodes and vertebrates alike and are activated by both the onset and removal of mechanical loads. Although tactile sensing organs differ across species, their response dynamics are remarkably similar and all depend on force transfer across the skin for activation of mechano-electrical transduction (MeT) channels in sensory endings. In C. elegans , the native MeT channel is a mec-4 dependent, amiloride-sensitive DEG/ENaC/ASIC channel that is thought to be mechanically gated by a “force-from-filament” extracellular matrix (ECM)-dependent mechanism. How the MeT complex is linked to the ECM and how that relates to channel gating is not fully understood. For instance, mec-1 and mec-9 encode secreted ECM proteins, which are required for activating MeT currents in vivo, localizing MEC-4 channels to discrete puncta within touch receptor neurons, and for aligning channel puncta with discrete laminin-nidogen ECM puncta. Point mutations in mec-1 have no effect on laminin-nidogen puncta but mislocalize MEC-4 channels and cause touch insensitivity. Collectively, these properties make MEC-1 and MEC-9 ideal candidates to link MEC-4 to the ECM. Given that MEC-4 is constitutively active when expressed in Xenopus oocytes but not in vivo, we hypothesized that (1) co-expressing MEC-4 with MEC-1, MEC-9, or both proteins in Xenopus oocytes might reconstruct channel-matrix interactions and that (2) such an effect could close the channel. Here, we find that co-expression of MEC-1 or MEC-9 with MEC-4 decreases amiloride-sensitive current amplitude, consistent with the idea that co-expression reduces channel activity. We also found that degradation of the ECM by chymotrypsin reverses this effect. This suggests that both the decrease in baseline current and increase in protease sensitivity are consequences of increased channel to ECM coupling, and MEC-1 and MEC-9 can act as critical linker proteins.
Nors et al. (Sun,) studied this question.