Reconstitution of synaptic junctions orchestrated by teneurin-latrophilin complexes.

Publisher: American Association for the Advancement of Science Country of Publication: United States NLM ID: 0404511 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1095-9203 (Electronic) Linking ISSN: 00368075 NLM ISO Abbreviation: Science Subsets: MEDLINE

Publication: : Washington, DC : American Association for the Advancement of Science
Original Publication: New York, N.Y. : [s.n.] 1880-

Synapses*/metabolism ; Nerve Tissue Proteins*/metabolism ; Nerve Tissue Proteins*/chemistry ; Receptors, Peptide*/metabolism ; Receptors, Peptide*/chemistry; Animals ; Mice ; Protein Domains ; Humans ; Receptors, G-Protein-Coupled

Synapses are organized by trans-synaptic adhesion molecules that coordinate assembly of pre- and postsynaptic specializations, which, in turn, are composed of scaffolding proteins forming liquid-liquid phase-separated condensates. Presynaptic teneurins mediate excitatory synapse organization by binding to postsynaptic latrophilins; however, the mechanism of action of teneurins, driven by extracellular domains evolutionarily derived from bacterial toxins, remains unclear. In this work, we show that only the intracellular sequence, a dimerization sequence, and extracellular bacterial toxin-derived latrophilin-binding domains of Teneurin-3 are required for synapse organization, suggesting that teneurin-induced latrophilin clustering mediates synaptogenesis. Intracellular Teneurin-3 sequences capture liquid-liquid phase-separated presynaptic active zone scaffolds, enabling us to reconstitute an entire synaptic junction from purified proteins in which trans-synaptic teneurin-latrophilin complexes recruit phase-separated pre- and postsynaptic specializations.

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R01 MH126929 United States MH NIMH NIH HHS

0 (Nerve Tissue Proteins)
0 (Receptors, Peptide)
0 (LPHN3 protein, mouse)
0 (alpha-latrotoxin receptor)
0 (Receptors, G-Protein-Coupled)

Date Created: 20250117 Date Completed: 20250117 Latest Revision: 20250211

20250211

PMC11808628

10.1126/science.adq3586

39818903