Nimpf

We study the biology of LDL receptor related proteins (VLDL receptor and ApoER2), a group of cell surface receptors which mediate transport of macromolecules across cell membranes and play important roles in signal transduction. The biological systems we are working with are the chicken oocyte and the mammalian brain. These two systems reflect the functional dichotomy of the receptors which function in endocytosis (follicles) and signal transduction (brain development). The

We study the biology of LDL receptor related proteins (VLDL receptor and ApoER2), a group of cell surface receptors which mediate transport of macromolecules across cell membranes and play important roles in signal transduction. The biological systems we are working with are the chicken oocyte and the mammalian brain. These two systems reflect the functional dichotomy of the receptors which function in endocytosis (follicles) and signal transduction (brain development). The best characterized function of VLDLR in follicles of egg laying species is endocytosis of yolk precursors into the growing oocyte. These yolk precursors (VLDL and Vitellogenin) are synthesized in the liver and rapidly taken up by the growing oocyte. Recently we have started to elucidate cell signalling functions of VLDLR and ApoER2 in granulosa cells which support the maturation of oocytes within the follicle. In respect to brain development both receptors act as Reelin-signal transducers. The Reelin signal orchestrates the correct positioning of newly generated neurons within laminated structures of the brain.

In the development of the olfactory system in rodents the structure of olfactory bulb depends on neurons generated throughout life in the subventricular zone. These neurons migrate via the rostral migratory stream towards the olfactory bulb. This migration also depends on the presence of ApoER2 and VLDLR but seems to be independent on Reelin. To this end we have characterized thrombospondin-1 as novel ligand for ApoEr2 and VLDLR present in the rostral migratory stream. Currently we are focusing on the search for other alternative ligands for the receptors which are involved in orchestrating the migration of neuroblasts and/or which are involved in maturation of the follicle.