A stomatin-domain protein essential for touch sensation in the mouse

Abstract

Touch and mechanical pain are first detected at our largest sensory surface, the skin. The cell bodies of sensory neurons that detect such stimuli are located in the dorsal root ganglia, and subtypes of these neurons are specialized to detect specific modalities of mechanical stimuli. Molecules have been identified that are necessary for mechanosensation in invertebrates but so far not in mammals. In Caenorhabditis elegans, mec-2 is one of several genes identified in a screen for touch insensitivity and encodes an integral membrane protein with a stomatin homology domain. Here we show that about 35% of skin mechanoreceptors do not respond to mechanical stimuli in mice with a mutation in stomatin-like protein 3 (SLP3, also called Stoml3), a mammalian mec-2 homologue that is expressed in sensory neurons. In addition, mechanosensitive ion channels found in many sensory neurons do not function without SLP3. Tactile-driven behaviours are also impaired in SLP3 mutant mice, including touch-evoked pain caused by neuropathic injury. SLP3 is therefore indispensable for the function of a subset of cutaneous mechanoreceptors, and our data support the idea that this protein is an essential subunit of a mammalian mechanotransducer.

Laminin-332 coordinates mechanotransduction and growth cone bifurcation in sensory neurons

“…Using whole-cell, patch-clamp techniques we directly recorded mechanosensitive currents in cultured sensory neurons [12][13][14][15][16][17][18][19][20] . We first asked whether co-culture of sensory neurons with different cellular components of the skin can modulate the activity of mechanosensitive currents.…”

“…We first asked whether co-culture of sensory neurons with different cellular components of the skin can modulate the activity of mechanosensitive currents. When sensory neurons are cultured on a laminin substrate, standardly-derived from Engelbreth-Holm-Swarm cells (EHS matrix, henceforth referred to as laminin), more than 90% of the cells exhibit a mechanosensitive current evoked using a small (~740 nm displacement) stimulus to the neurite 12,[14][15] . At least three types of mechanosensitive current can be measured in sensory neurons, classified according to their inactivation time constant τ 1 , rapidly-adapting (RA, τ 1 <5 ms), intermediately-adapting (IA, τ 1 <50 ms) and slowly-adapting (SA, no adaptation during a 230 ms stimulus), (Fig.…”

ASIC3 Channels in Multimodal Sensory Perception

“…A stomatin-domain protein essential for touch sensation in the mouse, the stomatinlike protein 3 (SLP3), has been shown to associate in vitro with ASIC3, but not TRPV1, a control sensory ion channel (75). SLP3 inhibits the endogenous proton-gated currents mediated by ASICs in sensory neurons (75), suggesting the involvement of ASIC3 in mechanosensory complexes. Recently, asic3 -/-mice and their WT counterparts were exposed to a novel stroking stimulus to test sensitivity to dynamic mechanical stimulation (76).…”

Acid-sensing Ion Channels in Sensory Perception

“…Disruption of ASIC2 has a mixed effect whereas ASIC3 knockout mice have a markedly decreased mechanosensitivity in almost all classes of visceral afferents, indicating a clear positive effect (26). Recently, a protein indispensable for the function of a subset of cutaneous mechanoreceptors in mouse, the stomatin-like protein 3 (SLP3), has been shown to associate in vitro with ASIC2a, ASIC2b, and ASIC3 and to inhibit the endogenous proton-gated currents in HEK-293 cells and in sensory neurons (28). All these data strongly suggest a participation of ASICs in mechanotransduction.…”