Stomatin, a MEC-2 like protein, is expressed by mammalian sensory neurons.

The molecular mechanism whereby vertebrate primary sensory neurons convert mechanical energy at their receptive fields into action potentials is unknown. In recent years, genetic screens for touch insensitive mutants of the nematode worm Caenorhabditis elegans have led to the identification of several genes required for mechanical sensitivity. A model has been proposed in which a mechanically gated ion channel is connected both to the extracellular matrix and to the cytoskeleton. Displacement of the membrane is proposed to produce a shearing force that pulls the channel open. MEC-2 is thought to play an important role in this complex by linking the ion channel to the cytoskeleton. MEC-2 is highly homologous to a vertebrate protein called stomatin. Stomatin was first isolated from erythrocytes where it is a major integral membrane protein. To date, however, no data on neuronal expression of stomatin in the peripheral nervous system (PNS) or central nervous system (CNS) is available. Here, we have used RT-PCR, in situ hybridization, Northern blotting, and immunocytochemistry to demonstrate that stomatin is expressed by all sensory neurons in mouse dorsal root ganglia. Indirect immunofluorescence together with transfection of cultured adult sensory neurons with epitope-tagged stomatin show that stomatin is localized in spots on somatic and axonal membranes. During development, stomatin begins to be expressed by sensory neurons only as target innervation occurs. The onset of expression of stomatin thus coincides with the onset of functional mechanical sensitivity. Together, our data suggest that stomatin, like the C. elegans MEC-2 gene, is expressed in an appropriate temporal and spatial manner to participate in a putative vertebrate mechanotransduction complex.

The mammalian sodium channel BNC1 is required for normal touch sensation.

Of the vertebrate senses, touch is the least understood at the molecular level The ion channels that form the core of the mechanosensory complex and confer touch sensitivity remain unknown. However, the similarity of the brain sodium channel 1 (BNC1) to nematode proteins involved in mechanotransduction indicated that it might be a part of such a mechanosensor. Here we show that disrupting the mouse BNC1 gene markedly reduces the sensitivity of a specific component of mechanosensation: low-threshold rapidly adapting mechanoreceptors. In rodent hairy skin these mechanoreceptors are excited by hair movement. Consistent with this function, we found BNC1 in the lanceolate nerve endings that lie adjacent to and surround the hair follicle. Although BNC1 has been proposed to have a role in pH sensing, the acid-evoked current in cultured sensory neurons and the response of acid-stimulated nociceptors were normal in BNC1 null mice. These data identify the BNC1 channel as essential for the normal detection of light touch and indicate that BNC1 may be a central component of a mechanosensory complex.