Nature Communications· 2026Q1
Ternary Neurexin-T178-PTPR complexes represent a pre-synaptic core-module of neuronal synapse organization
- 3citations
- Q1SCImago
- 2026year
Short summary
Researchers identified a core pre-synaptic protein module composed of Neurexins, T178 tetraspanins, and PTPRs that organizes neuronal synapses.
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Key points
- A core pre-synaptic module comprising Neurexins, T178 tetraspanins (T178A/B), and LAR-type PTPRs was identified in the mouse brain.
- These ternary complexes assemble via their transmembrane domains during ER biogenesis.
- Loss of T178B destabilizes the module, reduces LAR-PTPRs, and re-distributes synaptic Neurexins.
- The module links pre-synaptic active zones to post-synaptic receptors, organizing trans-synaptic protein networks.
AI-generated from the title and abstract; the full text is not read.
Abstract
Abstract Synapses, prototypic sites for neuronal communication, are key to brain function. Their organization and properties are instructed by synaptic cell adhesion molecules (sCAMs) that may operate independently or in coordination through yet unknown linker proteins. Here, we used multi-epitope affinity-purifications combined with quantitative mass spectrometry and immuno-EM to comprehensively map synaptic protein networks in the mouse brain. We identify a pre-synaptic core-module assembled from the major sCAMs, Neurexins1-3 and LAR-type receptor protein-tyrosine-phosphatases (PTPRs), and the previously uncharacterized tetraspanins T178A/B. These ternary Neurexin-T178-PTPR complexes form through their trans-membrane domains and assemble during biogenesis in the ER. Loss of T178B leads to module destabilization, accompanied by strong reduction of LAR-PTPRs and re-distribution of synaptic Neurexins. At synapses, the Neurexin-T178-PTPR module recruits stable trans-synaptic protein networks thereby interlinking machineries of the pre-synaptic active zone and establishing stable associations with post-synaptic neurotransmitter receptors. This work uncovers a widely distributed core-module for synaptic adhesion and trans-synaptic signaling in the mammalian brain.
The authors' abstract, as published at the source. Nature Communications, 2026 · DOI ↗
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Field: Molecular Biology
Molecular BiologyBiochemistry, Genetics and Molecular Biology