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High N-glycan multiplicity is critical for neuronal adhesion and sensitizes the developing cerebellum to N-glycosylation defect

Proper brain development relies highly on protein N-glycosylation to sustain neuronal migration, axon guidance and synaptic physiology. Impairing the N-glycosylation pathway at early steps produces broad neurological symptoms identified in congenital disorders of glycosylation. However, little is kn...

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Hauptverfasser: Medina-Cano, Daniel (VerfasserIn) , Ucuncu, Ekin (VerfasserIn) , Nguyen, Lam Son (VerfasserIn) , Nicouleau, Michael (VerfasserIn) , Lipecka, Joanna (VerfasserIn) , Bizot, Jean-Charles (VerfasserIn) , Thiel, Christian (VerfasserIn) , Foulquier, François (VerfasserIn) , Lefort, Nathalie (VerfasserIn) , Faivre-Sarrailh, Catherine (VerfasserIn) , Colleaux, Laurence (VerfasserIn) , Guerrera, Ida Chiara (VerfasserIn) , Cantagrel, Vincent (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 12 October 2018
In: eLife
Year: 2018, Jahrgang: 7
ISSN:2050-084X
DOI:10.7554/eLife.38309
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.7554/eLife.38309
Volltext
Verfasserangaben:Daniel Medina-Cano, Ekin Ucuncu, Lam Son Nguyen, Michael Nicouleau, Joanna Lipecka, Jean-Charles Bizot, Christian Thiel, François Foulquier, Nathalie Lefort, Catherine Faivre-Sarrailh, Laurence Colleaux, Ida Chiara Guerrera, Vincent Cantagrel
Beschreibung
Zusammenfassung:Proper brain development relies highly on protein N-glycosylation to sustain neuronal migration, axon guidance and synaptic physiology. Impairing the N-glycosylation pathway at early steps produces broad neurological symptoms identified in congenital disorders of glycosylation. However, little is known about the molecular mechanisms underlying these defects. We generated a cerebellum specific knockout mouse for Srd5a3, a gene involved in the initiation of N-glycosylation. In addition to motor coordination defects and abnormal granule cell development, Srd5a3 deletion causes mild N-glycosylation impairment without significantly altering ER homeostasis. Using proteomic approaches, we identified that Srd5a3 loss affects a subset of glycoproteins with high N-glycans multiplicity per protein and decreased protein abundance or N-glycosylation level. As IgSF-CAM adhesion proteins are critical for neuron adhesion and highly N-glycosylated, we observed impaired IgSF-CAM-mediated neurite outgrowth and axon guidance in Srd5a3 mutant cerebellum. Our results link high N-glycan multiplicity to fine-tuned neural cell adhesion during mammalian brain development.
Beschreibung:Gesehen am 25.03.2020
Beschreibung:Online Resource
ISSN:2050-084X
DOI:10.7554/eLife.38309

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