Neuroligin-3 and Neuroligin-4X form Nanoscopic clusters and regulate growth cone organization and size

Nick J. F. Gatford; Michael Deans; Rodrigo R.R. Duarte; George Chennell; Katherine Sellers; Pooja Raval; Deepak Srivastava

doi:https://doi.org/10.1093/hmg/ddab277

Neuroligin-3 and Neuroligin-4X form Nanoscopic clusters and regulate growth cone organization and size

Nick J. F. Gatford, Michael Deans, Rodrigo R.R. Duarte, George Chennell, Katherine Sellers, Pooja Raval, Deepak Srivastava

Research output: Contribution to journal › Article › peer-review

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 (PAK1) 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.

Original language	English
Journal	Human Molecular Genetics
DOIs	https://doi.org/10.1093/hmg/ddab277
Publication status	Published - 20 Sept 2021

Access to Document

https://doi.org/10.1093/hmg/ddab277

Cite this

@article{6f26bd81b6dd492389fbc7bbff923211,

title = "Neuroligin-3 and Neuroligin-4X form Nanoscopic clusters and regulate growth cone organization and size",

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 (PAK1) 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.",

author = "Gatford, {Nick J. F.} and Michael Deans and Duarte, {Rodrigo R.R.} and George Chennell and Katherine Sellers and Pooja Raval and Deepak Srivastava",

year = "2021",

month = sep,

day = "20",

doi = "https://doi.org/10.1093/hmg/ddab277",

language = "English",

journal = "Human Molecular Genetics",

issn = "0964-6906",

publisher = "Oxford University Press",

}

TY - JOUR

T1 - Neuroligin-3 and Neuroligin-4X form Nanoscopic clusters and regulate growth cone organization and size

AU - Gatford, Nick J. F.

AU - Deans, Michael

AU - Duarte, Rodrigo R.R.

AU - Chennell, George

AU - Sellers, Katherine

AU - Raval, Pooja

AU - Srivastava, Deepak

PY - 2021/9/20

Y1 - 2021/9/20

N2 - 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 (PAK1) 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.

AB - 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 (PAK1) 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.

U2 - https://doi.org/10.1093/hmg/ddab277

DO - https://doi.org/10.1093/hmg/ddab277

M3 - Article

SN - 0964-6906

JO - Human Molecular Genetics

JF - Human Molecular Genetics

ER -

Neuroligin-3 and Neuroligin-4X form Nanoscopic clusters and regulate growth cone organization and size

Abstract

Access to Document

Other files and links

Fingerprint

Cite this