Conserved basal lamina proteins, laminin and nidogen, are repurposed to organize mechanosensory complexes responsible for touch sensation

Abstract

SummaryThe sense of touch is conferred by the conjoint function of somatosensory neurons and skin cells. These cells meet across a gap filled by a basal lamina, an ancient structure found in all metazoans. Using Caenorhabditis elegans nematodes, we show that mechanosensory complexes essential for touch sensation reside at this interface and contain laminin, nidogen, and the MEC-4 mechano-electrical transduction channel proteins. These proteins fail to coalesce into discrete, stable structures in dissociated neurons and in touch-insensitive mec-1, mec-9 and mec-5 secreted ECM protein mutants. MEC-4, but not laminin or nidogen, is destabilized in animals where somatosensory neurons secrete MEC-1 carrying missense mutations in the C-terminal Kunitz domain. Thus, neuron-epithelial cell interfaces are instrumental in mechanosensory complex assembly and function. Drawing on computational modeling, we propose that these complexes concentrate mechanical stress into discrete foci and they enhance touch sensitivity. Consistent with this idea, loss of nidogen reduces the density of mechanoreceptor complexes, the amplitude of the touch-evoked currents they carry, and touch sensitivity in parallel. These findings imply that somatosensory neurons secrete proteins that actively repurpose the basal lamina to generate special-purpose mechanosensory complexes responsible for vibrotactile sensing.