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During embryonic brain development the Reelin signaling pathway orchestrates correct positioning of neurons in laminated structures of the brain. This pathway starts with binding of Reelin to two receptors ApoER2 and VLDL receptor and leads to phosphorylation of the intracellular adapter protein Dab1. This straight forward concept, however, is much more complex than originally anticipated. Reelin binding induces higher order clusters of the receptors and depending upon which receptor is present in these clusters the outcome of the signal differs. In addition, both receptors are expressed as differentially spliced and glycosylated variants in specific subsets of neurons. The main aim of our research is to describe the actual signalosome(s) formed and to characterize their specific functions.
To investigate the formation of specific signalosomes by Reelin we use time-resolved anisotropy (homo-FRET) and fluorescence lifetime imaging microscopy (FLIM-FRET).
Johannes Nimpf graduated from the Technical University of Graz (Austria). After 2 years as Assistant Prof. at the Medical University in Graz he spent 6 years at the University of Alberta in Edmonton (Canada). In 1992 he moved to Vienna to became Associate Prof. at the Medical University of Vienna. Since 2009 he is Chair of the Division of Molecular Genetics.
We recently discovered that the initial event of the Reelin signaling pathway is the formation of higher order receptor clusters on the surface of target neurons. Dlugosz et al. Front. Mol. Neurosci. 12:53. doi: 10.3389/fnmol.2019.00053
Thrombospondin-1 was discovered in our laboratory as ligand for ApoER2 and VLDL receptor. The signal created by this interaction guides neuroblasts along the rostral migratory stream to form the olfactory bulb during embryonic brain development. Blake et al. EMBO J. 27, 3069 - 3080, 2008
Enzymes involved in hepatic acylglycerol metabolism in the chicken.
Riegler, Barbara; Besenboeck, Carolin; Bauer, Raimund; Nimpf, Johannes; Schneider, Wolfgang J
Differential functions of ApoER2 and VLDL receptor in Reelin signaling depend on differential sorting of the receptors.
Duit, Sarah; Mayer, Harald; Blake, Sophia M; Schneider, Wolfgang Johann; Nimpf, Johannes
The E3 ubiquitin ligase IDOL induces the degradation of the low density lipoprotein receptor family members VLDLR and ApoER2.
Hong, Cynthia; Duit, Sarah; Jalonen, Pilvi; Out, Ruud; Scheer, Lilith; Sorrentino, Vincenzo; Boyadjian, Rima; Rodenburg, Kees W; Foley, Edan; Korhonen, Laura; Lindholm, Dan; Nimpf, Johannes; van Berkel, Theo J C; Tontonoz, Peter; Zelcer, Noam