title: A LewisX glycoprotein screen identifies the low density lipoprotein receptor-related protein 1 (LRP1) as a modulator of oligodendrogenesis in mice.
abstract: In the developing and adult CNS multipotent neural stem cells reside in distinct niches. Specific carbohydrates and glycoproteins are expressed in these niche microenvironments which are important regulators of stem cell maintenance and differentiation fate. LewisX (LeX), also known as stage-specific embryonic antigen-1 or CD15, is a defined carbohydrate moiety expressed in niche microenvironments of the developing and adult CNS. LeX-glycans are involved in stem cell proliferation, migration, and stemness. A few LeX carrier proteins are known, but a systematic analysis of the targets of LeX glycosylation in vivo has not been performed so far. Using LeX glycosylation as a biomarker we aimed to discover new glycoproteins with a potential functional relevance for CNS development. By immunoaffinity chromatography we enriched LeX glycoproteins from embryonic and postnatal mouse brains and used one-dimensional nLC-ESI-MS/MS for their identification. We could validate phosphacan, tenascin-C, and L1-CAM as major LeX carrier proteins present in vivo. Furthermore, we identified LRP1, a member of the LDL receptor family, as a new LeX carrier protein expressed by mouse neural stem cells. Surprisingly, little is known about LRP1 function for neural stem cells. Thus, we generated Lrp1 knock-out neural stem cells by Cre-mediated recombination and investigated their properties. Here, we provide first evidence that LRP1 is necessary for the differentiation of neural stem cells toward oligodendrocytes. However, this function is independent of LeX glycosylation.
authors.affiliation: Departments of Cell Morphology and Molecular Neurobiology, D-44780 Bochum, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Hennen
authors.affiliation: Departments of Cell Morphology and Molecular Neurobiology, D-44780 Bochum, Germany.
authors.forename: Dina
authors.initials: D
authors.lastname: Safina
authors.affiliation: Plant Biochemistry, Ruhr-University Bochum, D-44780 Bochum, Germany.
authors.forename: Ute
authors.initials: U
authors.lastname: Haussmann
authors.affiliation: Stem Cell Engineering Group, Institute of Reconstructive Neurobiology, University of Bonn-Life and Brain Center, D-53105 Bonn, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Wörsdörfer
authors.affiliation: Stem Cell Engineering Group, Institute of Reconstructive Neurobiology, University of Bonn-Life and Brain Center, D-53105 Bonn, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Edenhofer
authors.affiliation: Plant Biochemistry, Ruhr-University Bochum, D-44780 Bochum, Germany.
authors.forename: Ansgar
authors.initials: A
authors.lastname: Poetsch
authors.affiliation: Departments of Cell Morphology and Molecular Neurobiology, D-44780 Bochum, Germany. Electronic address: andreas.faissner@rub.de.
authors.forename: Andreas
authors.initials: A
authors.lastname: Faissner
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation; D006031:Glycosylation; D016256:Lewis X Antigen / Q000235:genetics / Q000378:metabolism*; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D039842:Neural Cell Adhesion Molecule L1 / Q000235:genetics / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism*; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5 / Q000235:genetics / Q000378:metabolism; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism*; D019063:Tenascin / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D016256:Lewis X Antigen; D026503:Low Density Lipoprotein Receptor-Related Protein-1; C486645:Lrp1 protein, mouse; D009419:Nerve Tissue Proteins; D039842:Neural Cell Adhesion Molecule L1; D011973:Receptors, LDL; D019063:Tenascin; D025521:Tumor Suppressor Proteins; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5
keywords: Carbohydrate; Development; Differentiation; Extracellular Matrix Proteins; Glycoprotein; Lipoprotein-like Receptor (LRP); Neural Stem Cell