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Neuroligin-3 and neuroligin-4X form nanoscopic clusters and regulate growth cone organization and size.
Gatford, Nicholas J F; Deans, P J Michael; Duarte, Rodrigo R R; Chennell, George; Sellers, Katherine J; Raval, Pooja; Srivastava, Deepak P.
Affiliation
  • Gatford NJF; Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology, & Neuroscience, King's College London, London, UK.
  • Deans PJM; MRC Centre for Neurodevelopmental Disorders, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
  • Duarte RRR; Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology, & Neuroscience, King's College London, London, UK.
  • Chennell G; MRC Centre for Neurodevelopmental Disorders, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
  • Sellers KJ; Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology, & Neuroscience, King's College London, London, UK.
  • Raval P; Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology, & Neuroscience, King's College London, London, UK.
  • Srivastava DP; Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology, & Neuroscience, King's College London, London, UK.
Hum Mol Genet ; 31(5): 674-691, 2022 03 03.
Article in En | MEDLINE | ID: mdl-34542148
ABSTRACT
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Growth Cones / Autism Spectrum Disorder Limits: Humans Language: En Journal: Hum Mol Genet Journal subject: BIOLOGIA MOLECULAR / GENETICA MEDICA Year: 2022 Document type: Article Affiliation country: Reino Unido
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Growth Cones / Autism Spectrum Disorder Limits: Humans Language: En Journal: Hum Mol Genet Journal subject: BIOLOGIA MOLECULAR / GENETICA MEDICA Year: 2022 Document type: Article Affiliation country: Reino Unido