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


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 domain1. 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.

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Figure 1: Mechanically insensitive primary afferents.
Figure 2: SLP3 is required for the expression of mechanosensitive currents in subsets of DRG neurons.
Figure 3: Association of SLP3 with ASIC ion channels.
Figure 4: Tactile driven behaviour is altered in SLP3 mutant mice.


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We thank A. Scheer, H. Thränhardt and K. Borgwald for technical support; G. Kempermann for advice on confocal microscopy and the rotorod test; and C. Birchmeier, A. Hammes, I. Ibanez-Tallon and T. Willnow for helpful comments on the manuscript. The Deutsche Forschungsgemeinschaft provided grant support. J.H. was supported by a von Humboldt fellowship.

Author Contributions C.W., J.H. and G.R.L. performed electrophysiological experiments on SLP3 mutants. D.R. and A.B. generated the SLP3 mutant. C.W. characterized the SLP3 mouse. L.H. and C.W. performed the behavioural experiments. A.E. and R.M. performed biochemical interaction studies, and O.C. and P.H. characterized SLP3 effects in HEK-293 cells. A.B. cloned the rat SLP3 cDNA. J.H. and A.K. conducted rescue experiments. B.E. performed electron microscopy. H.M. and D.L. conducted neuropathic pain measurements in the SLP3 mutant mice. G.R.L. conceived and planned experimental studies with help from C.W. and P.A.H. G.R.L. wrote the paper.

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Correspondence to Gary R. Lewin.

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Wetzel, C., Hu, J., Riethmacher, D. et al. A stomatin-domain protein essential for touch sensation in the mouse. Nature 445, 206–209 (2007).

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