Title :

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

Author(s) :

Medina-Cano, D. [Auteur]
Morphogenèse du cœur - Heart morphogenesis [Imagine - Institut Pasteur U1163]
Ucuncu, Ekin [Auteur]
Nguyen, Lam [Auteur]
Institut de chimie et procédés pour l'énergie, l'environnement et la santé [ICPEES]
Nicouleau, Michael [Auteur]
Imagine - Institut des maladies génétiques [IMAGINE - U1163]
Lipecka, Joanna [Auteur]
CHU Trousseau [APHP]
Bizot, Jean-Charles [Auteur]
Thiel, Christian [Auteur]
JRC Institute for Energy and Transport [IET]
Foulquier, Francois [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Lefort, Nathalie [Auteur]
Faivre-Sarrailh, Catherine [Auteur]
Institut de Neurobiologie de la Méditerranée [Aix-Marseille Université] [INMED - INSERM U1249]
Colleaux, Laurence [Auteur]
Imagine - Institut des maladies génétiques [IMAGINE - U1163]
Guerrera, Ida C [Auteur]
Structure Fédérative de Recherche Necker [SFR Necker - UMS 3633 / US24]
Cantagrel, Vincent [Auteur]
Imagine - Institut des maladies génétiques [IMAGINE - U1163]

Journal title :

eLife

Publication date :

2018

Keyword(s) :

Science du vivant
neurosciences

HAL domain(s) :

Chimie/Chimie théorique et/ou physique

English abstract : [en]

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 ...
Show more >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.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

CNRS
Université de Lille

Collections :

• Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576

Research team(s) :

Mécanismes moléculaires de la N-glycosylation et pathologies associées

Submission date :

2020-02-12T15:45:53Z
2024-02-23T10:16:48Z