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nencki.gov.pl » Working Groups » Department of Cell Biology »
Laboratory of Plasma Membrane Receptors

Head
Andrzej SOBOTA

Staff
Maciej CZERKIES (PhD student), Monika HEREĆ, Szczepan JÓZEFOWSKI, Magdalena KULMA (PhD student), Katarzyna KWIATKOWSKA, Anna ŁUKASIK (PhD student), Agata SAMONEK (PhD student), Ewelina SZYMAŃSKA (PhD student), Kazimiera MROZIŃSKA (technician)

Research profile

Our research is focused on mechanisms of signal generation by immunoreceptors of macrophages and monocytes that are involved in phagocytosis and inflammatory responses. We have chosen to elucidate signaling pathways behind FcγRIIA-mediated uptake of pathogen and TLR2- and TLR4-dependent responses to microbial cell wall components such as LPS and LAM. The essential approach is to examine how the activated receptors initiate cascade of events leading to reorganization of membrane constituents, activation of tyrosine kinases and phosphoinositide kinases. In particular, studied are: the involvement of plasma membrane rafts in immunoreceptor signaling, the role of the sphingomyelin cycle and ceramide generation in the transduction of signals by the receptor, the role of PI(4,5)P2 in modulation of submembrane cytoskeleton and in internalization of membrane-associated particles.

Current research activities

  • examination of mechanisms governing an association of activated Fcγ receptor IIA  and Toll-like receptors with rafts of the plasma membrane – an engagement of acid sphingomyelinase and ceramide; our approaches range from gene silencing through immunoassays to enzymatic analysis;

  • plasma membrane rafts as centers of PIP5-kinase activation and PIP2 turnover; expression of PIP5-kinase and its fragments is performed to reveal how the kinase is recruited to the plasma membrane;

  • studies on the molecular composition of detergent-resistant membrane domains (DRM) and how it affects a raft involvement in the immunoreceptors signaling;

  • exploration of suitability of lysenin – sphingomyelin-binding protein, as a tool for studies of sphingomyelin-cycle during Fcγ receptor activation; the mechanism of interaction of lysenin with sphingomyelin in membranes is studied by variety of biophysical approaches, including ATR-FTIR, monolayer studies and FRET assays;

  • ultrastructural studies on participation of plasma membrane domains (rafts) in signal generation by Fcγ receptor IIA and Toll-like receptor 2 and 4;

  • studies of the effect of Fcγ receptors activation on organization of cortical actin cytoskeleton during the receptor-mediated phagocytosis.

Selected publications

Szymańska E., Sobota A., Czuryło E., Kwiatkowska K. (2008) Expression of PI(4,5)P2-binding proteins lowers the PI(4,5)P2 level and inhibits FccRIIA-mediated cell spreading and phagocytosis. Eur. J. Immunol. 38: 260–272.

Hereć M., Gagoś M., Kulma M., Kwiatkowska K., Sobota A., Gruszecki W. (2008) Secondary structure and orientation of the pore-forming toxin lysenin in a sphingomyelin-containing membrane. Biochimica et Biophysica Acta 1778: 872–879

Sobota A., Strzelecka-Kiliszek A., Gladkowska E., Yoshida K., Mrozinska K., Kwiatkowska K. (2005) Binding of IgG-opsonized particles to FcγR is an active stage of phagocytosis that involves receptor clustering and phosphorylation. J. Immunol. 175: 4450-4457

Abdel Shakor AB., Kwiatkowska K., Sobota A. (2004) Cell surface ceramide generation precedes and controls FcγRII clustering and phosphorylation in rafts. J.Biol.Chem. 279: 36778-36787

Korzeniowski, M., Kwiatkowska, K. and Sobota, A. (2003) Insights into the association of FcγRII and TCR with detergent-resistant membrane domains: isolation of the domains in detergent-free density gradients facilitates membrane fragment reconstitution. Biochemistry 42: 5358-5367


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Published at: 2008-05-27 10:03
 

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