will take place on Tuesday, March 15, 2016 from 17:15 to 18:15 in Lecture Hall H1, Turmgebäude.
Host: Prof. Markus Schwaninger
Institute of Experimental and Clinical Pharmacology and Toxicology
Universität zu Lübeck
Abstract
Lysosomal sphingolipid degradation requires the presence of water-soluble hydrolases, SAPs, anionic phospholipids like BMP, and an acidic pH value. Inherited defects of catabolic hydrolases or SAPs cause various sphingolipidoses. SAPs are membrane-perturbing proteins which facilitate sphingolipid digestion by presenting insoluble lipid molecules to soluble catabolic enzymes. SAPs (the GM2-activator and saposins A-D) bind to lipid bilayers, mobilize and solubilize lipids at acidic pH values. As demonstrated by plasmon resonance studies for saposins A , B and GM2AP, low cholesterol levels and increasing concentrations of BMP favour lipid extraction and membrane disintegration. The inherited absence of all four saposins (A-D) causes a perinatal fatal membrane and sphingolipid storage disease, also disrupting the water permeability barrier of the skin.
Ongoing in vitro studies indicate that plasma membrane stabilizing lipids, i.e. sphingomyelin and cholesterol, inhibit several steps of lysosomal sphingolipid and glycosphingolipid catabolism, lipid solubilisation and intervesicular (glyco-) lipid transfer activities of several SAPs and NPC2, even in the presence of activating anionic phospholipids. Reconstitution experiments indicate that anionic lipids are essential for the catabolism of membrane bound ganglioside GM2, the main storage compound of Tay-Sachs disease.
CV
Konrad Sandhoff completed his PhD in Biochemistry from LMU in Munich. After research stays in Munich, Israel and the USA he became a full professor of biochemistry at the University of Bonn in 1979. Since 2007 he is a senior professor at the LIMES institute, Bonn. Major Research Interests: Molecular life sciences: analysis and pathobiochemistry of lysosomal (glyco-) sphingolipid storage diseases, structure and function of lysosomal enzymes and lipid binding proteins, topology of endocytosis and glycolipid metabolism, regulation of glycolipid biosynthesis. He has published more than 480 peer-reviewed papers. He has received more than 15 renowned national and international awards.
