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SUMMARY:Membrane rafts in immunoreceptor signaling - reality vs. artefacts
  - Professor Vaclav Horejsi\, The Institute of Molecular Genetics\, Prague
DTSTART:20111102T123000Z
DTEND:20111102T133000Z
UID:TALK32732@talks.cam.ac.uk
CONTACT:Sue Griffin
DESCRIPTION:Membrane (lipid) rafts\, microdomains enriched in glycosphingo
 lipids\, cholesterol\, glycosylphosphatidylinositol-anchored proteins\, Sr
 c-family kinases\, several transmembrane adaptor proteins and G-proteins a
 nd markedly resistant to solubilization by certain detergents\, appear to 
 play important roles in early phases of immunoreceptor signaling\, but als
 o in regulation of a number of other receptors. Biological importance and 
 even the very existence of rafts has been repeatedly questioned\, as they 
 are difficult to visualize by current microscopic techniques and most info
 rmation on them comes from biochemical studies in detergent lysates. \n\nF
 or a long time there has been a discussion on the relevance of the deterge
 nt-resistant membrane microdomains (DRMs) to the native membrane rafts.  I
 deally\, the DRMs should closely correspond to the native membrane microdo
 mains before solubilization. However\, this ideal situation may be more or
  less far from reality\, because the detergent may induce various types of
  artefacts. \n\nWe believe that many of such problems are due to the use o
 f Triton-X100 in most studies. Even at low temperatures\, this detergent a
 ctually gradually dissolves DRMs and does not yield stable products. On th
 e other hand\, Brij-98 is much better in this respect – the properties a
 nd composition of DRMs obtained when using it are almost independent of te
 mperature and detergent concentration. \n\nOur data indicate that under th
 ese conditions leukocyte membranes yield a mixture of DRMs\, differing in 
 their protein composition\, buoyant density and sensitivity to cholesterol
  depletion. These different types of DRMs appear to correspond to function
 ally different native membrane microdomains. \n\nWe believe that the curre
 nt skepticism concerning the usefulness of DRMs is exaggerated and the bio
 chemical approach should be rehabilitated. Under optimal conditions\, DRMs
  may actually be as useful as various detergent-resistant multi-subunit re
 ceptor complexes.\n\nRelevant recent papers from our laboratory:\n\nDraber
  P\, Vonkova I\, Stepanek O\, Hrdinka M\, Kucova M\, Skopcova T\, Otahal P
 \, Angelisova P\, Horejsi V\, Yeung M\, Weiss A\, Brdicka T.\nSCIMP: trans
 membrane adaptor protein involved in MHCII signaling.\nMol Cell Biol. 2011
  Sep 19. [Epub ahead of print]\n\nHrdinka M\, Dráber P\, Stepanek O\, Orm
 sby T\, Otahal P\, Angelisova P\, Brdicka T\, Paces J\, Horejsi V\, Drbal 
 K.\nPRR7 is a transmembrane adaptor protein expressed in activated T cells
  involved in regulation of T cell receptor signaling and apoptosis.\nJ Bio
 l Chem. 2011\;286(22):19617-29.\n\nOtahal P\, Pata S\, Angelisová P\, Hor
 ejsi V\, Brdicka T.\nThe effects of membrane compartmentalization of csk o
 n TCR signaling.\nBiochim Biophys Acta. 2011\;1813(2):367-76. \n\nOtahal P
 \, Angelisova P\, Hrdinka M\, Brdicka T\, Novak P\, Drbal K\, Horejsi V.\n
 A new type of membrane raft-like microdomains and their possible involveme
 nt in TCR signaling.\nJ Immunol. 2010\;184(7):3689-96.\n
LOCATION:Lecture Theatre\, Department of Pathology\, Tennis Court Road
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