Research Report 2010 - MDC

Gary R. LewinStructure of the GroupGroup LeaderProf. Dr. Gary R. LewinScientistsDr. Jing Hu*Dr. Alexey KozlenkovDr. Stefan LechnerDr Nevena Milenkovic*Dr Simone Pifferi*Dr Kate PooleDr. Ewan St. John SmithMolecular Physiology of SomaticSensationSomatic sensation includes all those sensations that we consciously feel after stimulation ofthe body, e.g. touch, warmth, cooling, or even limb movement. We experience thesesensations as a direct result of the activation of sensory neurons that are located in the dorsalroot ganglia (DRG). In our group we are interested in the molecular mechanisms that allowthese neurons to transduce these varied stimuli. Sensory neurons can, for example, detectchanges in temperature of the skin in non-noxious (not painful) as well as the noxious range(painful heat, or cold). They can also detect gentle movement of the skin as well as intensemechanical stimulation of the skin that is normally harmful. The nature of the transductionmolecules involved together with the developmental events that lead to specification of theappropriate sensory neuron sub-types are actively investigated the lab.Molecular Basis of MechanotransductionYinth Andrea Bernal-Sierra, Liudmilla Lapatsina, StefanLechner, Alexey KozlenkovMechanotransduction is the process whereby receptorproteins present in the endings of sensory neurons areable to detect mechanical stimulation of the tissuethey innervate. We have used information from geneticexperiments with the nematode worm C.elegans toidentify possible vertebrate candidate proteins thatmight detect mechanical stimuli. Genetic screens fortouch insensitive worms have turned up around 15genes whose function is necessary to confer touch sensitivity.These genes were named mec for mechanicallyinsensitive and we have focused on identifying a rolemammalian orthologs of these genes in touch sensation.The mec genes in C.elegans have been proposed towork together in a mechanotransduction complex. Anessential component of this complex is the membraneprotein MEC-2 that forms a hairpin in the membraneand might regulate the activity of the mechanotransducingchannel. We have cloned new vertebrateshomologues of mec genes and have created mousemutant alleles to characterize the in vivo function ofthese genes. MEC-2 is a member of a large family ofproteins that contain a stomatin-like domain. A memberof this family called SLP3 (stomatin like protein-3)was cloned by our group, and we subsequently generateda mouse model with a null mutation of the SLP3locus. In SLP3 mutant mice many mechanoreceptors (ortouch receptors) in the skin do not work in the absenceof the SLP3 protein. In order to analyze touch sensationin mice we also developed a novel behavioral assay fortouch driven behavior in rodents. This assay is based onthe ability of mice to detect and react to gratings, whichare fine enough to have a textured quality.We were verypleased to find that SLP3 mutant mice have severedeficits in their ability to detect such textured surfaces.Current work in the lab focuses on the role of relatedmembers of the stomatin-domain family in mechanotransduction,structure function studies and the identificationof further essential interaction partners forSLP3.162 Function and Dysfunction of the Nervous System