Mammalian somatosensory mechanotransduction

Abstract

In the mammalian somatosensory system, mechanosensitive neurons mediate the senses of touch and pain. Among sensory modalities, mechanosensation has been the most elusive with regard to the identification of transduction molecules. One factor that has hindered the identification of transduction molecules is the diversity of neurons; physiological studies have revealed many subtypes of neurons, specialized to detect a variety of mechanical stimuli. Do different subtypes use the same transduction molecules that are modified by cellular context? Or, are there multiple mechanotransducers that specialize in sensing different mechanical stimuli? This review highlights recent progress in identifying and characterizing candidate molecular force transducers, as well as the development of new tools to characterize touch transduction at the molecular, cellular, and behavioral levels.

Figure 1

Cation channels implicated in mechanosensory transduction. (a) Proposed topology of Deg/ENaC and TRP channels; cylinders indicate predicted transmembrane domains and bold loops indicate putative pore regions. TRP channels have a variable number of amino-terminal ankyrin repeats (see glossary; red). (b) In C. elegans, TRPV channels (purple) are thought to transduce nose touch and hypertonic shock. Deg/ENaC subunits (cyan) have been proposed to transduce body touch and to act in proprioception [5]. In Drosophila, TRPV, TRPN (orange) and TRPA (orange) subunits are candidate mechanotransduction channels in bristles, which mediate touch and proprioception, in chordotonal organs, which mediate hearing and proprioception, and in multidendritic neurons, which respond to harsh mechanical and thermal stimuli. The Deg/ENaC channel Pickpocket1 has been implicated in larval proprioception [5]. (c) A schematic of the mammalian somatosensory system shows DRG neurons projecting to skin and spinal cord. Deg/ENaC and TRP channels are expressed in different classes of somatosensory neurons, the cell bodies of which are indicated by circles in the DRG. C nociceptors (green) and Aδ afferents (pink) have free nerve endings; light touch receptors (Aβ; black) include Merkel cell–neurite complexes (red), lanceolate endings around hair follicles (gray), and Pacinian corpuscles (dark blue spiral).