title: 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.
authors.affiliation: Department of Neuroscience, Max-Delbrück Center for Molecular Medicine and Charité Universitätsmedizin Berlin, Robert-Rössle-Strasse 10, 13125 Berlin-Buch, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Wetzel
authors.forename: Jing
authors.initials: J
authors.lastname: Hu
authors.forename: Dieter
authors.initials: D
authors.lastname: Riethmacher
authors.forename: Anne
authors.initials: A
authors.lastname: Benckendorff
authors.forename: Lena
authors.initials: L
authors.lastname: Harder
authors.forename: Andreas
authors.initials: A
authors.lastname: Eilers
authors.forename: Rabih
authors.initials: R
authors.lastname: Moshourab
authors.forename: Alexey
authors.initials: A
authors.lastname: Kozlenkov
authors.forename: Dominika
authors.initials: D
authors.lastname: Labuz
authors.forename: Ombretta
authors.initials: O
authors.lastname: Caspani
authors.forename: Bettina
authors.initials: B
authors.lastname: Erdmann
authors.forename: Halina
authors.initials: H
authors.lastname: Machelska
authors.forename: Paul A
authors.initials: PA
authors.lastname: Heppenstall
authors.forename: Gary R
authors.initials: GR
authors.lastname: Lewin
mesh_terms: D062565:Acid Sensing Ion Channels; D000344:Afferent Pathways; D000818:Animals; D004553:Electric Conductivity; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism; D008297:Male; D008465:Mechanoreceptors / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry* / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D051381:Rats; D015222:Sodium Channels / Q000378:metabolism; D014110:Touch / Q000502:physiology*
chemical_list: D062565:Acid Sensing Ion Channels; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D015222:Sodium Channels; C461699:Stoml3 protein, mouse