Neuroligin-3 and neuroligin-4X form nanoscopic clusters and regulate growth cone organization and size.
Journal
Human molecular genetics
ISSN: 1460-2083
Titre abrégé: Hum Mol Genet
Pays: England
ID NLM: 9208958
Informations de publication
Date de publication:
03 03 2022
03 03 2022
Historique:
received:
20
07
2021
revised:
25
08
2021
accepted:
13
09
2021
pubmed:
21
9
2021
medline:
28
4
2022
entrez:
20
9
2021
Statut:
ppublish
Résumé
The cell-adhesion proteins neuroligin-3 and neuroligin-4X (NLGN3/4X) have well described roles in synapse formation. NLGN3/4X are also expressed highly during neurodevelopment. However, the role these proteins play during this period is unknown. Here we show that NLGN3/4X localized to the leading edge of growth cones where it promoted neuritogenesis in immature human neurons. Super-resolution microscopy revealed that NLGN3/4X clustering induced growth cone enlargement and influenced actin filament organization. Critically, these morphological effects were not induced by autism spectrum disorder (ASD)-associated NLGN3/4X variants. Finally, actin regulators p21-activated kinase 1 and cofilin were found to be activated by NLGN3/4X and involved in mediating the effects of these adhesion proteins on actin filaments, growth cones and neuritogenesis. These data reveal a novel role for NLGN3 and NLGN4X in the development of neuronal architecture, which may be altered in the presence of ASD-associated variants.
Identifiants
pubmed: 34542148
pii: 6372551
doi: 10.1093/hmg/ddab277
pmc: PMC8895740
doi:
Substances chimiques
Cell Adhesion Molecules, Neuronal
0
Membrane Proteins
0
Nerve Tissue Proteins
0
neuroligin 3
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
674-691Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/N026063/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 097819
Pays : United Kingdom
Informations de copyright
© The Author(s) 2021. Published by Oxford University Press.
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