Reelin mobilizes a VAMP7-dependent synaptic vesicle pool and selectively augments spontaneous neurotransmission

Neuron. 2013 Nov 20;80(4):934-46. doi: 10.1016/j.neuron.2013.08.024. Epub 2013 Nov 7.

Abstract

Reelin is a glycoprotein that is critical for proper layering of neocortex during development as well as dynamic regulation of glutamatergic postsynaptic signaling in mature synapses. Here, we show that Reelin also acts presynaptically, resulting in robust rapid enhancement of spontaneous neurotransmitter release without affecting properties of evoked neurotransmission. This effect of Reelin requires a modest but significant increase in presynaptic Ca(2+) initiated via ApoER2 signaling. The specificity of Reelin action on spontaneous neurotransmitter release is encoded at the level of vesicular SNARE machinery as it requires VAMP7 and SNAP-25 but not synaptobrevin2, VAMP4, or vti1a. These results uncover a presynaptic regulatory pathway that utilizes the heterogeneity of synaptic vesicle-associated SNAREs and selectively augments action potential-independent neurotransmission.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apolipoproteins E / metabolism
  • Calcium Signaling / physiology
  • Cell Adhesion Molecules, Neuronal / genetics
  • Cell Adhesion Molecules, Neuronal / physiology*
  • Cells, Cultured
  • Electrophysiological Phenomena
  • Excitatory Postsynaptic Potentials / physiology
  • Extracellular Matrix Proteins / genetics
  • Extracellular Matrix Proteins / physiology*
  • Female
  • Lentivirus / genetics
  • Male
  • Mice
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / physiology*
  • Patch-Clamp Techniques
  • Phosphatidylinositol 3-Kinases / metabolism
  • R-SNARE Proteins / genetics
  • R-SNARE Proteins / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • SNARE Proteins / metabolism
  • Serine Endopeptidases / genetics
  • Serine Endopeptidases / physiology*
  • Synaptic Transmission / physiology*
  • Synaptic Vesicles / physiology*
  • Synaptosomal-Associated Protein 25 / genetics
  • Synaptosomal-Associated Protein 25 / physiology
  • Tetrodotoxin / pharmacology

Substances

  • Apolipoproteins E
  • Cell Adhesion Molecules, Neuronal
  • Extracellular Matrix Proteins
  • Nerve Tissue Proteins
  • R-SNARE Proteins
  • SNARE Proteins
  • Snap25 protein, rat
  • Synaptosomal-Associated Protein 25
  • Vamp7 protein, rat
  • Tetrodotoxin
  • Serine Endopeptidases
  • reelin protein