Synaptic neurexin-1 assembles into dynamically regulated active zone nanoclusters.
ADAM10 Protein
/ metabolism
Animals
Calcium-Binding Proteins
/ metabolism
Cell Adhesion Molecules, Neuronal
/ metabolism
Cells, Cultured
Epitopes
/ metabolism
HEK293 Cells
Humans
Mice, Inbred C57BL
Nanoparticles
/ chemistry
Neural Cell Adhesion Molecules
/ metabolism
Neurons
/ metabolism
Presynaptic Terminals
/ metabolism
Protein Isoforms
/ metabolism
Proteolysis
Synapses
/ metabolism
Journal
The Journal of cell biology
ISSN: 1540-8140
Titre abrégé: J Cell Biol
Pays: United States
ID NLM: 0375356
Informations de publication
Date de publication:
05 08 2019
05 08 2019
Historique:
received:
13
12
2018
revised:
10
05
2019
accepted:
30
05
2019
pubmed:
3
7
2019
medline:
19
5
2020
entrez:
3
7
2019
Statut:
ppublish
Résumé
Neurexins are well-characterized presynaptic cell adhesion molecules that engage multifarious postsynaptic ligands and organize diverse synapse properties. However, the precise synaptic localization of neurexins remains enigmatic. Using super-resolution microscopy, we demonstrate that neurexin-1 forms discrete nanoclusters at excitatory synapses, revealing a novel organizational feature of synaptic architecture. Synapses generally contain a single nanocluster that comprises more than four neurexin-1 molecules and that also includes neurexin-2 and/or neurexin-3 isoforms. Moreover, we find that neurexin-1 is physiologically cleaved by ADAM10 similar to its ligand neuroligin-1, with ∼4-6% of neurexin-1 and ∼2-3% of neuroligin-1 present in the adult brain as soluble ectodomain proteins. Blocking ADAM10-mediated neurexin-1 cleavage dramatically increased the synaptic neurexin-1 content, thereby elevating the percentage of Homer1(+) excitatory synapses containing neurexin-1 nanoclusters from 40-50% to ∼80%, and doubling the number of neurexin-1 molecules per nanocluster. Taken together, our results reveal an unexpected nanodomain organization of synapses in which neurexin-1 is assembled into discrete presynaptic nanoclusters that are dynamically regulated via ectodomain cleavage.
Identifiants
pubmed: 31262725
pii: jcb.201812076
doi: 10.1083/jcb.201812076
pmc: PMC6683742
doi:
Substances chimiques
Calcium-Binding Proteins
0
Cell Adhesion Molecules, Neuronal
0
Epitopes
0
Neural Cell Adhesion Molecules
0
Nrxn1 protein, mouse
0
Protein Isoforms
0
neuroligin 1
0
ADAM10 Protein
EC 3.4.24.81
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
2677-2698Subventions
Organisme : NIMH NIH HHS
ID : R37 MH052804
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH052804
Pays : United States
Organisme : NIMH NIH HHS
ID : F32 MH105040
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG047366
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM122487
Pays : United States
Organisme : NIMH NIH HHS
ID : U19 MH114830
Pays : United States
Commentaires et corrections
Type : CommentIn
Type : ErratumIn
Informations de copyright
© 2019 Trotter et al.
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