N-glycoproteomics of brain synapses and synaptic vesicles.

CP: Neuroscience N-glycan congenital disorders of glycosylation fucose glycosylation membrane trafficking plasma membrane synapse synaptic vesicle

Journal

Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691

Informations de publication

Date de publication:
25 04 2023
Historique:
received: 19 07 2022
revised: 13 01 2023
accepted: 23 03 2023
medline: 4 10 2023
pubmed: 11 4 2023
entrez: 10 4 2023
Statut: ppublish

Résumé

At mammalian neuronal synapses, synaptic vesicle (SV) glycoproteins are essential for robust neurotransmission. Asparagine (N)-linked glycosylation is required for delivery of the major SV glycoproteins synaptophysin and SV2A to SVs. Despite this key role for N-glycosylation, the molecular compositions of SV N-glycans are largely unknown. In this study, we combined organelle isolation techniques and high-resolution mass spectrometry to characterize N-glycosylation at synapses and SVs from mouse brain. Detecting over 2,500 unique glycopeptides, we found that SVs harbor a distinct population of oligomannose and highly fucosylated N-glycans. Using complementary fluorescence methods, we identify at least one highly fucosylated N-glycan enriched in SVs compared with synaptosomes. High fucosylation was characteristic of SV proteins, plasma membrane proteins, and cell adhesion molecules with key roles in synaptic function and development. Our results define the N-glycoproteome of a specialized neuronal organelle and inform timely questions in the glycobiology of synaptic pruning and neuroinflammation.

Identifiants

pubmed: 37036808
pii: S2211-1247(23)00379-0
doi: 10.1016/j.celrep.2023.112368
pmc: PMC10560701
mid: NIHMS1895595
pii:
doi:

Substances chimiques

Glycoproteins 0
Polysaccharides 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

112368

Subventions

Organisme : NIMH NIH HHS
ID : R25 MH086466
Pays : United States
Organisme : NHGRI NIH HHS
ID : T32 HG002760
Pays : United States
Organisme : NIGMS NIH HHS
ID : P41 GM108538
Pays : United States
Organisme : NINDS NIH HHS
ID : R35 NS097362
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Organisme : NIMH NIH HHS
ID : F30 MH116580
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM140935
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH061876
Pays : United States

Informations de copyright

Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests J.J.C. is a consultant for Thermo Fisher Scientific, Seer, and 908 Devices.

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Auteurs

Mazdak M Bradberry (MM)

Department of Chemistry, University of Wisconsin-Madison, Madison, WI 53706, USA; Department of Biomolecular Chemistry, University of Wisconsin-Madison, Madison, WI 53706, USA; National Center for Quantitative Biology of Complex Systems, Madison, WI 53706, USA; Howard Hughes Medical Institute and Department of Neuroscience, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA; Department of Psychiatry, Columbia University, New York, NY 10032, USA. Electronic address: mazdak.bradberry@nyspi.columbia.edu.

Trenton M Peters-Clarke (TM)

Department of Chemistry, University of Wisconsin-Madison, Madison, WI 53706, USA; Department of Biomolecular Chemistry, University of Wisconsin-Madison, Madison, WI 53706, USA; National Center for Quantitative Biology of Complex Systems, Madison, WI 53706, USA.

Evgenia Shishkova (E)

Department of Chemistry, University of Wisconsin-Madison, Madison, WI 53706, USA; Department of Biomolecular Chemistry, University of Wisconsin-Madison, Madison, WI 53706, USA; National Center for Quantitative Biology of Complex Systems, Madison, WI 53706, USA.

Edwin R Chapman (ER)

Howard Hughes Medical Institute and Department of Neuroscience, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA.

Joshua J Coon (JJ)

Department of Chemistry, University of Wisconsin-Madison, Madison, WI 53706, USA; Department of Biomolecular Chemistry, University of Wisconsin-Madison, Madison, WI 53706, USA; National Center for Quantitative Biology of Complex Systems, Madison, WI 53706, USA; Morgridge Institute for Research, Madison, WI 53715, USA.

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