MDGAs are fast-diffusing molecules that delay excitatory synapse development by altering neuroligin behavior.
Electrophysiology
adhesion molecules
cell biology
hippocampal cultures
neuroscience
rat
single molecule tracking
synapse development
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
09 05 2022
09 05 2022
Historique:
received:
03
11
2021
accepted:
11
04
2022
entrez:
9
5
2022
pubmed:
10
5
2022
medline:
11
5
2022
Statut:
epublish
Résumé
MDGA molecules can bind neuroligins and interfere with trans-synaptic interactions to neurexins, thereby impairing synapse development. However, the subcellular localization and dynamics of MDGAs, or their specific action mode in neurons remain unclear. Here, surface immunostaining of endogenous MDGAs and single molecule tracking of recombinant MDGAs in dissociated hippocampal neurons reveal that MDGAs are homogeneously distributed and exhibit fast membrane diffusion, with a small reduction in mobility across neuronal maturation. Knocking-down/out MDGAs using shRNAs and CRISPR/Cas9 strategies increases the density of excitatory synapses, the membrane confinement of neuroligin-1, and the phosphotyrosine level of neuroligins associated with excitatory post-synaptic differentiation. Finally, MDGA silencing reduces the mobility of AMPA receptors, increases the frequency of miniature EPSCs (but not IPSCs), and selectively enhances evoked AMPA-receptor-mediated EPSCs in CA1 pyramidal neurons. Overall, our results support a mechanism by which interactions between MDGAs and neuroligin-1 delays the assembly of functional excitatory synapses containing AMPA receptors.
Identifiants
pubmed: 35532105
doi: 10.7554/eLife.75233
pii: 75233
pmc: PMC9084894
doi:
pii:
Substances chimiques
Cell Adhesion Molecules, Neuronal
0
Nerve Tissue Proteins
0
Receptors, AMPA
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Déclaration de conflit d'intérêts
AT, ML, GB, BT, SD, AF, IC, KV, JV, MS, Jd, DC, OT No competing interests declared
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