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

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

Publication date: Sep 20, 2021

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.

Concepts Keywords
Kinase Cytoskeleton
Nanoscopic Actin
Neurodevelopment Developmental neuroscience
Nlgn4x Cell biology
Unknown Molecular neuroscience
Proteins
Branches of biology
Microfilament
ADF/Cofilin family
Growth cone
Neuroligin

Semantics

Type Source Name
disease MESH growth
disease MESH autism spectrum disorder

Original Article

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