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Evaluation of Synaptic Multiplicity Using Whole-cell Patch-clamp Electrophysiology
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Turbocharging synaptic transmission.

James E Rothman1, Kirill Grushin1, Manindra Bera1

  • 1Nanobiology Institute and Department of Cell Biology, Yale University, New Haven, CT, USA.

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|August 29, 2023
PubMed
Summary
This summary is machine-generated.

Synaptotagmin rings coordinate synaptic vesicle release by organizing SNAREpins. Peripheral SNAREpins, boosted by Complexin, accelerate neurotransmitter release for rapid synaptic transmission.

Keywords:
Munc13SNAREpinsintra-vesicular pressureneurotransmitter releasesynaptophysin

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Biochemistry

Background:

  • Synaptotagmin is implicated in synaptic vesicle (SV) clamping and release.
  • Synchronous neurotransmission relies on precise SV fusion.
  • SNARE proteins mediate membrane fusion.

Purpose of the Study:

  • To elucidate the structural organization and functional role of SNAREpins in SV release.
  • To investigate the contribution of peripheral SNAREpins to the speed of neurotransmitter release.

Main Methods:

  • Biochemical assays
  • Genetic analysis
  • Electron microscopy
  • Cell-free system measurements

Main Results:

  • A ring of 12 SNAREpins per SV, with six central and six peripheral.
  • Central SNAREpins directly bind Synaptotagmin and are Ca++-sensitive.
  • Peripheral SNAREpins, bridged by Complexin, enhance fusion speed.
  • Synaptophysin hexamers contribute VAMP to both SNAREpin types.

Conclusions:

  • Synaptotagmin-organized SNAREpins control SV fusion.
  • Peripheral SNAREpins and Complexin 'turbocharge' neurotransmitter release.
  • This mechanism explains rapid synchronous neurotransmission.