A09 - Scaffolding of mechanotransduction domains in migratinfg and non-migrating cells

Principal Investigators

Prof. Dr. Gary R. Lewin, MDC

Dr. Annette Hammes-Lewin, MDC

Little is known about the formation and molecular composition of the mechanosensitive domains in the plasma membrane of mammalian somatosensory neurons. We hypothesise that the stomatin-like protein-3 (SLP3/ STOML3) functions as a scaffold to organise these mechanosensitive domains, and modulates the activity of mechanosensitive channels through cellular contacts with the extracellular environment.

We are combining standard electrophysiological, biochemical and genetic approaches with super-resolution light microscopy. We are also developing an innovative new biophysical technique to characterize the role of STOML3 in the formation, molecular composition and function of mechanosensitive domains and their  modulation by the extracellular matrix.

References:

  • C. Wetzel, J. Hu, D. Riethmacher, A. Benckendorff, L. Harder, A. Eilers, R. Moshourab, A. Kozlenkov, D. Labuz, O. Caspani, B. Erdmann, H. Machelska, P.A. Heppenstall & G.R. Lewin. A stomatin-domain protein essential for touch sensation in the mouse.  (2007) Nature 445, 206–9.

  • L.Y. Chiang, K. Poole, B.E. Oliveira, N. Duarte, Y.A. Bernal Sierra, L. Bruckner-Tuderman, M. Koch, J. Hu& G.R. Lewin. Laminin-332 coordinates mechanotransduction and growth cone bifurcation in sensory neurons.  (2011) Nat. Neurosci. 14, 993–1000.

  • L. Lapatsina, J. Brand, K. Poole, O. Daumke & G.R. Lewin. Stomatin-domain proteins.  (2011) Eur. J. Cell Biol. 91, 240–245.

  • L. Lapatsina, J.A. Jira, E. St. J. Smith, K. Poole, A. Kozlenkov, D. Bilbao, G.R. Lewin and P.A. Heppenstall Regulation of ASIC channels by a stomatin/STOML3 complex located in a mobile vesicle pool in sensory neurons.  (2012) Open Biology doi:10.1098/rsob.120096

  • J. Brand, E. St J. Smith, D. Schwefel, L. Lapatsina, K. Poole, D. Omerbašić, A. Kozlenkov, J. Behlke, G.R. Lewin and O. Daumke. A Stomatin Dimer Modulates the Activity of Acid-sensing Ion Channels. (2012) The EMBO Journal 31: 3635–3646.