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Selected examples of the function of cell surface glycans:physiology and pathology of specific glycoproteins |
Short introduction into the different types of glycans and their principle of biosynthesis. Examples for plasma membrane N-glycan structures. Cell type-specific expression of N-glycans. General functions of cell surface N-glycans. Structure, biosynthesis and function in cell adhesion during development, differentiation and malignant transformation of polysialic acid of NCAM. Molecular basis of protein-specificity of polysialyltransferases. Phenotypic and functional consequences of NCAM and polysialyltransferase knock out in mice. General aspects of O-glycan cell and tissue expression and biological functions. Tn and T antigen structure and biosynthesis. Chaperone control of T synthase. Tn syndrome and carcinoma-associated Tn/T antigen expression and Cosmic somatic mutations. Importance for angiogenesis, lymphangiogenesis and liver function of T synthase. |
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Roth J, Taatjes DJ, Wagner P, Weisgerber C, Heitz PU, Goridis C, Bitter-Suermann D (1988) Reexpression of poly(sialic acid) units of the neural cell adhesion molecule in Wilms tumor. Proc Natl Acad Sci USA 85:2999-3003Weinhold B, Seidenfaden R, Rockle I, Muhlenhoff M, Schertzinger F, Conzelmann S, Marth JD, Gerardy-Schahn R, Hildebrandt H (2005) Genetic ablation of polysialic acid causes severe neurodevelopmental defects rescued by deletion of the neural cell adhesion molecule. J Biol Chem 280:42971-42977 |
Presentation and discussion of two publications demonstrating the importance of polysialic acid of the neural cell adhesion molecule NCAM for brain development and function, and in malignant tumors. |
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Aryal RP, Ju T, Cummings RD (2010) The endoplasmic reticulum chaperone Cosmc directly promotes in vitro folding of T-synthase. J Biol Chem 285:2456-2462Fu J, Gerhardt H, McDaniel JM, Xia B, Liu X, Ivanciu L, Ny A, Hermans K, Silasi-Mansat R, McGee S, Nye E, Ju T, Ramirez MI, Carmeliet P, Cummings RD, Lupu F, Xia L (2008) Endothelial cell O-glycan deficiency causes blood/lymphatic misconnections and consequent fatty liver disease in mice. J Clin Invest 118:3725-3737 |
Presentation and discussion of two publications on the importance of a single chaperone for assembly and activity of T synthase and the function of the T antigen in angiogenesis |
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Formation and dynamics of post-Golgi apparatus carriers.Constitutive secretion. Sorting in the TGN: membrane proteins and lipids. |
Concept of epithelial cell polarity. Structure and function of the TGN. The different types of TGN-derived post-Golgi transport carriers. Molecular structure and formation of clathrin coats. Dynamin and formation of clathrin-coated vesicles. Clathrin coat disassembly. Principle of constitutive secretion as exemplified by albumin. Techniques and cells for the study of formation and movement of post-Golgi transport carriers. Molecular basis of formation and fission of Golgi tubules. Principles of apical and basolateral sorting and underlying molecular mechanisms. Experimental manipulation of post-Golgi traffic. |
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Deborde S, Perret E, Gravotta D, Deora A, Salvarezza S, Schreiner R, Rodriguez-Boulan E (2008) Clathrin is a key regulator of basolateral polarity. Nature 452:719-723 |
Presentation and discussion of a publication about the importance of clathrin for basolateral polarity. |
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Delacour D, Greb C, Koch A, Salomonsson E, Leffler H, Le Bivic A, Jacob R (2007)Apical sorting by galectin-3-dependent glycoprotein clustering. Traffic 8:379-388 |
Presentation and discussion of a publication on the importance of galctin-3 mediated protein clustering for apical sorting. |
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Endocytosis: receptor-mediated endocytosis via clathrin-coated pits. Molecular biology of clathrin coats. Caveolar and non-caveolar endocytosis. Molecular biology and cell type-specificity of caveolins. |
Cellular distribution and function of clathrin-coated structures. Structure, molecular composition and formation of clathrin-coated pits and clathrin-coated vesicles. Adaptor proteins for clathrin-coated pits. Fission process and dynamin action. Mechanochemistry of clathrin-coat endocytosis. Mechanism of action of PIP2 hydrolysis. Clathrin-coated pit and clathrin-coated plaqiue formation and composition. Caveolae-mediated endocytosis. Structure and composition of caveolae. Molecular biology of caveolins and biogenesis of caveolae. Cavin proteins. Formation and function of caveosomes. Role of caveolae in signalling, endothelial cell biology and muscle diseases. |
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Loerke D, Mettlen M, Yarar D, Jaqaman K, Jaqaman H, Danuser G, Schmid SL (2009) Cargo and dynamin regulate clathrin-coated pit maturation. PLoS Biol 7:e57 |
Presentation and discusssion of a scientific publication on the importance of dynamin and endocytotic cargo for maturation of clathrin-coated pits. |
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Zhu Y, Xu J, Heinemann SF (2009) Two pathways of synaptic vesicle retrieval revealed by single-vesicle imaging. Neuron 61:397-411 |
Presentation and discusssion of a scientific publication on different pathways of membrane retrieval following exocytosis. |
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Endosome formation and types of endosomes.Endocytotic pathways taken by pathogens and toxins. |
The initial stages of endocytoss by clathrin-coated elements such as coated pit, coated invagination and coated vesicles and their relation to endosomes. Endocytotic routes to the TGN, Golgi apparatus and endoplasmic reticulum. Structure and molecular composition of early endosomes and function in recycling. Detection of early endosomes by immunofluorescence. Receptor-ligand dissociation in receycling endosomes. Structure and membrane protein composition of tubular pericentriolar endosomes. Birbeck granules of Langerhans cells and antigen presentation. Glucose transporter and recycling endosomes. Multivesicular bodies: structure, formation/maturation. Formation of MVB vesicles by inward budding through ESCRT complexes. ESCRT interaction with membrane lipids and proteins. Importance of monubiquitylation for endocytosis. Endocytosis of toxins and pathogens and traffic to the Golgi apparatus and cytosol. |
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Endosome formation and types of endosomes.Endocytotic pathways taken by pathogens and toxins. |
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Guerra L, Teter K, Lilley BN, Stenerlow B, Holmes RK, Ploegh HL, Sandvig K, Thelestam M, Frisan T (2005) Cellular internalization of cytolethal distending toxin: a new end to a known pathway. Cell Microbiol 7:921-934 |
Presentation and discusssion of a scientific publication on the mode of entry and action of a cytotxic toxin. |
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Transcytosis in epithelial cells and endothelial cells. Endocytic routes and the fate of endocytosed macromolecules and receptors. |
Principles and cellular aspects of transcytosis. Importance of transcytosis as defense mechanism against infection. Transcytosis, processing, receptor interaction and secretion of dimeric IgA. Transcytosis of IgG, receptor interaction, and importance for postnatal immune defense. Transcytosis by endothelial cells. Albumin transcytosis by caveolae of endothelia and its regulation by gp60, caveolin-1 and Src. Albumin-mediated transcytosis of myeloperoxidase. Receptor-mediated endocytosis of LDL, LDL-LDL receptor structure and molecular basis for interaction. Mechanism and regulation of LDL endocytosis. Metabolism of endocytosed LDL. LDL receptor, mutaions and atherosclerosis |
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Transcytosis in epithelial cells and endothelial cells. Endocytic routes and the fate of endocytosed macromolecules and receptors. |
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Eden ER, White IJ, Tsapara A, Futter CE (2010) Membrane contacts between endosomes and ER provide sites for PTP1B-epidermal growth factor receptor interaction. Nat Cell Biol 12:267-272 |
Presentation and discusssion of a scientific publication on signaling between endosomes and endoplasmic reticulum. |
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