Evolutionary tuning of complexin-synaptotagmin fusion clamp governs regulated neurotransmitter release

Clamping in both mammals and Caenorhabditis elegans requires combined action of Complexin (CPX) and Synaptotagmin-1 (Syt1), with neither alone sufficient.

• Why it matters: Opposite phenotypes from removing CPX or Syt1 across species leave unclear whether their fusion-clamp roles truly diverged or reflect species-specific tuning of a conserved mechanism.
• What they did: Using a reconstituted single-vesicle assay that isolates clamping from docking and priming, the study compared mammalian and C. elegans orthologs and tested CPX SNARE specificity and Syt1 intrinsic clamping strength.
• The result: CPX clamps only with its cognate SNARE complex via its accessory helix, while Syt1 ortholog differences in clamping strength map to C2B-driven higher-order oligomerization, setting CPX dependence and supporting sequential cooperative regulation.

AI summary of the abstract · may contain errors · not medical advice · read the paper.