TRR 13:  Membrane Microdomains and Their Role in Human Disease

• Subject Area: Biology
• Term: from 2004 to 2008
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5485945

Membrane microdomains play central roles in various biological processes, notably intracellular membrane trafficking and signal transduction. Thus, lipid rafts contribute to the formation of a signalling microenvironment in the plasma membrane, and hence are involved in cellular growth and differentiation. A number of signal transduction processes depend on lipid rafts. Paradigmatic examples include multi-chain immune recognition receptors such as the T-cell and B-cell antigen receptors and the high affinity receptor for IgE. Another key role of such membrane microdomains is related to the control of protein processing, with Alzheimer¿s disease being the most prominent example. The formation of membrane microdomains is a crucial aspect of various sorting events that take place during membrane trafficking. Moreover, lipid rafts have been implicated in membrane budding, fission and fusion.Many aspects of the molecular cell biology of membrane microdomains still need further investigation. These include the mechanisms of lipid raft formation, the molecular composition of different types of lipid rafts and the characterisation of specific, raft-forming proteins. This will eventually allow to address the role of membrane microdomains in human disease. In this context, the cell type-specific expression of membrane microdomains as well as the disease-specific expression of microdomain-associated proteins and their processing needs to be addressed. Given the functions of lipid rafts in the hematopoietic, immune and nervous system as well as their modulation by lipid metabolism, neurodegenerative and cardiovascular diseases are among the most intriguing targets for further analysis.The young field of membrane microdomains originated from research on the molecular biology of the cell. While it is one goal of this Transreginal Collaborative Research Centre to intensify this basic research, another is to form a bridge between basic and disease-oriented research with immediate clinical relevance. In this respect, both the basic research groups and the disease-oriented research groups at the three locations Dresden, Heidelberg and Regensburg constitute essential components of an integrated, highly complementary research network allowing the rapid transfer of results from basic research into the relevant clinical research disciplines. Finally, a high degree of additional synergy will be achieved by a group of technology projects.

• DFG Programme: CRC/Transregios

Completed projects

• A01 - Lipid raft clustering in Membrane trafficking (Project Head Simons, Kai )
• A02 - Membrane microdomain formation in artificial membrane systems (Project Head Steinem, Claudia )
• A03 - Crosstalk between the apo-A-I/ABCA1 pathway and lipid microdomains (Project Heads Drobnik, Wolfgang ;  Schmitz, Gerd )
• A04 - Lipid rafts and obesity: function of OBR-GRP and endospanin, two lipid raft-associated tetraspanins, in the leptin recceptor trafficking (Project Head Hoflack, Bernard )
• A08 - Specific Lipid Interactions of Transmembrane Segments of Membrane Proteins (Project Heads Brügger, Britta ;  Wieland, Felix Wilhelm Theodor )
• B01 - Physiological funkction of the cholesterol-interacting, lipid raft-associated plasma membrane protein prominin: from cell biology to human disease (Project Heads Corbeil, Denis ;  Huttner, Wieland B. )
• B02 - Investigation of molecular mechanisms responsible for the phenotype of caveolin-1 KO-mice (Project Head Kurzchalia, Teymuras )
• B03 - Caveolae as tracking as trafficking compartments to manage transcytosis within the alveolar epithelium (Project Head Kasper, Michael )
• C01 - Pathophysiological role of caveolae and caveolin in vascular proliferative disease (Project Heads Schwencke, Carsten ;  Strasser, Ruth H. )
• C02 - Intracellular lipid-trafficking as a potential crossroad in Aß-generation (Project Heads Beyreuther, Konrad ;  Hartmann, Tobias )
• C03 - Specific Lipid Interactions of Transmembrane Segments of Membrande Proteins (Project Heads Brügger, Britta ;  Wieland, Felix Wilhelm Theodor )
• C04 - Nef and Lipid Rafts: Functional Coordination of the HIV Pathogeneticity factor during particle release and TCR Signaling (Project Head Fackler, Ph.D., Oliver T. )
• C06 - The pathophysiological role of caveolae and caveolin -1 in cardiovascular disease: A new model of endothelial mediated cardiomyopathy (Project Heads Kasper, Michael ;  Strasser, Ruth H. )
• C08 - Crosstalk between the apoA-I/ABCA1 and apoE/ceramide pathway and the role of lipid microdomains (Project Head Schmitz, Gerd )
• D01 - Quantitative Profiling of Phospholipids and Glycolipids by Quadrupole Time-of-Flight Mass Spectrometry (Project Head Shevchenko, Andrej )
• D02 - Lipid fluorescence microscopy (Project Head Thiele, Christoph )
• D03 - Characterization of lipid-dependent conformation intermediates of raft-associatet proteins using NMR spectroscopy (Project Head Kalbitzer, Hans Robert )
• Z - Central administration and project coordinationof the Transregional Colloborative Research Center (Project Head Schmitz, Gerd )

• Applicant Institution: Universität Regensburg
• Co-Applicant Institution: Ruprecht-Karls-Universität Heidelberg; Technische Universität Dresden
• Participating Institution: Max-Planck-Institut für molekulare Zellbiologie und Genetik (MPI-CBG)
• Spokesperson: Professor Dr. Gerd Schmitz