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Updated: Aug 6, 2026

Presynapse Formation Assay Using Presynapse Organizer Beads and “Neuron Ball” Culture
Published on: August 2, 2019
Neurexin-1γ drives synaptic transmission through structural integration of neurotransmitter release machinery and
Nirmala Padmanabhan1, Rebecca E Twilley1, Shinichiro Oku1
1PrairieNeuro Research Centre, Kleysen Institute for Advanced Medicine, Health Sciences Centre, Winnipeg, MB R3E 0Z3, Canada; Department of Physiology and Pathophysiology, Max Rady College of Medicine, Rady Faculty of Health Sciences University of Manitoba, Winnipeg, MB R3E 0J9, Canada.
Abstract:
Synaptic transmission requires precise nanoscale alignment of presynaptic release machinery and postsynaptic receptor nanodomains. However, the molecular links bridging these subsynaptic elements remain unresolved. We identify mammalian neurexin-1γ as a presynaptic organizer that directly couples release sites to AMPAR nanodomains. Using complementary mouse lines, an epitope-tagged Nrxn1γ knockin and an Nrxn1γ knockout, and a multimodal approach, we find that neurexin-1γ is enriched at presynaptic release sites precisely opposite AMPAR nanoclusters. Nrxn1γ deletion perturbs synaptic nanoarchitecture, impairs vesicle docking and release, and disrupts transsynaptic nanocolumn alignment and AMPAR positioning, leading to broad deficits in both basal and evoked synaptic transmission, plasticity, and cognitive function. Mechanistically, neurexin-1γ directly binds AMPAR N-termini via its extracellular heparan sulfate glycans, anchoring them with nanoscale precision to neurotransmitter release sites. Our findings establish neurexin-1γ as a nanoscale transsynaptic bridge for optimal synaptic function and circuit activity, revealing an unconventional role for this minimal neurexin variant.
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