Stomatin and sensory neuron mechanotransduction.

Somatic sensory neurons of the dorsal root ganglia are necessary for a large part of our mechanosensory experience. However, we only have a good knowledge of the molecules required for mechanotransduction in simple invertebrates such as the nematode Caenorhabiditis elegans. In C. elegans, a number of so-called mec genes have been isolated that are required for the transduction of body touch. One such gene, mec-2 codes for an integral membrane protein of the stomatin family, a large group of genes with a stomatin homology domain. Using stomatin null mutant mice, we have tested the hypothesis that the founding member of this family, stomatin might play a role in the transduction of mechanical stimuli by primary sensory neurons. We used the in vitro mouse skin nerve preparation to record from a large population of low- and high-threshold mechanoreceptors with myelinated A-fiber (n = 553) and unmyelinated C-fiber (n = 157) axons. One subtype of mechanoreceptor, the d-hair receptor, which is a rapidly adapting mechanoreceptor, had reduced sensitivity to mechanical stimulation in the absence of stomatin. Other cutaneous mechanoreceptors, including nociceptive C-fibers were not affected by the absence of a functional stomatin protein. Patch-clamp analysis of presumptive D-hair receptor mechanoreceptive neurons, which were identified by a characteristic rosette morphology in culture, showed no change in membrane excitability in the absence of the stomatin protein. We conclude that stomatin is required for normal mechanotransduction in a subpopulation of vertebrate sensory neurons.

[1]  G. Lewin,et al.  The high threshold mechanotransducer: A status report , 2006, Pain.

[2]  C. Stucky,et al.  Stomatin, a MEC-2 Like Protein, Is Expressed by Mammalian Sensory Neurons , 1999, Molecular and Cellular Neuroscience.

[3]  C. Stucky,et al.  Receptive properties of mouse sensory neurons innervating hairy skin. , 1997, Journal of neurophysiology.

[4]  J. Sinard,et al.  Exclusion of the stomatin, α‐adducin and β‐adducin loci in a large kindred with dehydrated hereditary stomatocytosis , 1999 .

[5]  B. Dash,et al.  Isolation of cDNA coding for an ubiquitous membrane protein deficient in high Na+, low K+ stomatocytic erythrocytes. , 1992, Blood.

[6]  B. Dash,et al.  Isolation of cDNA coding for an ubiquitous membrane protein deficient in high Na+, low K+ stomatocytic erythrocytes , 1992 .

[7]  A. Iggo,et al.  A quantitative study of cutaneous receptors and afferent fibres in the cat and rabbit , 1967, The Journal of physiology.

[8]  M. Chalfie,et al.  MEC-2 regulates C. elegans DEG/ENaC channels needed for mechanosensation , 2002, Nature.

[9]  M. Chalfie,et al.  The MEC-4 DEG/ENaC channel of Caenorhabditis elegans touch receptor neurons transduces mechanical signals , 2005, Nature Neuroscience.

[10]  Rabih Moshourab,et al.  A stomatin-domain protein essential for touch sensation in the mouse , 2007, Nature.

[11]  I. Maurer-Fogy,et al.  Cloning and nucleotide sequence of cDNA encoding human erythrocyte band 7 integral membrane protein. , 1991, Biochimica et biophysica acta.

[12]  Y. Bertrand,et al.  A family showing recessively inherited multisystem pathology with aberrant splicing of the erythrocyte Band 7.2b ('stomatin') gene , 2004, Journal of Inherited Metabolic Disease.

[13]  B. Dash,et al.  Stomatin: a putative cation transport regulator in the red cell membrane. , 1993, Biochimica et biophysica acta.

[14]  J. Wemmie,et al.  Stomatin Modulates Gating of Acid-sensing Ion Channels* , 2004, Journal of Biological Chemistry.

[15]  Gary R Lewin,et al.  Mechanosensation and pain. , 2004, Journal of neurobiology.

[16]  Peter G. Gillespie,et al.  Molecular basis of mechanosensory transduction , 2001, Nature.

[17]  C. Stucky,et al.  GFR α2/neurturin signalling regulates noxious heat transduction in isolectin B4‐binding mouse sensory neurons , 2002, The Journal of physiology.

[18]  G. Lewin,et al.  A T-type calcium channel required for normal function of a mammalian mechanoreceptor , 2003, Nature Neuroscience.

[19]  R. Kerr,et al.  In Vivo Imaging of C. elegans Mechanosensory Neurons Demonstrates a Specific Role for the MEC-4 Channel in the Process of Gentle Touch Sensation , 2003, Neuron.

[20]  P. Cesare,et al.  A novel heat-activated current in nociceptive neurons and its sensitization by bradykinin. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[21]  A. Pizzey,et al.  Four new cases of stomatin‐deficient hereditary stomatocytosis syndrome: association of the stomatin‐deficient cryohydrocytosis variant with neurological dysfunction , 2004, British journal of haematology.

[22]  G. Lewin,et al.  Role of T-Type Calcium Current in Identified D-Hair Mechanoreceptor Neurons Studied In Vitro , 2004, The Journal of Neuroscience.

[23]  Martin Chalfie,et al.  The mechanosensory protein MEC-6 is a subunit of the C. elegans touch-cell degenerin channel , 2002, Nature.

[24]  Gary R Lewin,et al.  Mechanosensitive currents in the neurites of cultured mouse sensory neurones , 2006, The Journal of physiology.

[25]  H O Handwerker,et al.  Responsiveness and functional attributes of electrically localized terminals of cutaneous C-fibers in vivo and in vitro. , 1992, Journal of neurophysiology.

[26]  N Mohandas,et al.  Stomatocytosis is absent in "stomatin"-deficient murine red blood cells. , 1999, Blood.

[27]  Martin Chalfie,et al.  Genetics of sensory mechanotransduction. , 2002, Annual review of genetics.