TY - JOUR
T1 - A stomatin-domain protein essential for touch sensation in the mouse
AU - Wetzel, Christiane
AU - Hu, Jing
AU - Riethmacher, Dieter
AU - Benckendorff, Anne
AU - Harder, Lena
AU - Eilers, Andreas
AU - Moshourab, Rabih
AU - Kozlenkov, Alexey
AU - Labuz, Dominika
AU - Caspani, Ombretta
AU - Erdmann, Bettina
AU - Machelska, Halina
AU - Heppenstall, Paul A.
AU - Lewin, Gary R.
N1 - Funding Information:
Acknowledgements 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.
PY - 2007/1/11
Y1 - 2007/1/11
N2 - 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.
AB - 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.
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U2 - 10.1038/nature05394
DO - 10.1038/nature05394
M3 - Article
C2 - 17167420
AN - SCOPUS:33846259087
VL - 445
SP - 206
EP - 209
JO - Nature
JF - Nature
SN - 0028-0836
IS - 7124
ER -