title: Reelin mobilizes a VAMP7-dependent synaptic vesicle pool and selectively augments spontaneous neurotransmission.
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.
authors.affiliation: Department of Neuroscience, UT Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Manjot
authors.initials: M
authors.lastname: Bal
authors.forename: Jeremy
authors.initials: J
authors.lastname: Leitz
authors.forename: Austin L
authors.initials: AL
authors.lastname: Reese
authors.forename: Denise M O
authors.initials: DM
authors.lastname: Ramirez
authors.forename: Murat
authors.initials: M
authors.lastname: Durakoglugil
authors.forename: Joachim
authors.initials: J
authors.lastname: Herz
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Monteggia
authors.forename: Ege T
authors.initials: ET
authors.lastname: Kavalali
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D055724:Electrophysiological Phenomena; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000502:physiology*; D005260:Female; D016086:Lentivirus / Q000235:genetics; D008297:Male; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D018408:Patch-Clamp Techniques; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D050683:R-SNARE Proteins / Q000235:genetics / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000091042:Reelin Protein; D050600:SNARE Proteins / Q000378:metabolism; D012697:Serine Endopeptidases / Q000235:genetics / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*; D013572:Synaptic Vesicles / Q000502:physiology*; D050825:Synaptosomal-Associated Protein 25 / Q000235:genetics / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D001057:Apolipoproteins E; D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D019869:Phosphatidylinositol 3-Kinases; D050683:R-SNARE Proteins; D000091042:Reelin Protein; D050600:SNARE Proteins; D012697:Serine Endopeptidases; D050825:Synaptosomal-Associated Protein 25; D013779:Tetrodotoxin; C000717129:Reln protein, rat; C494210:Snap25 protein, rat; C496926:Vamp7 protein, rat; C000717128:Reln protein, mouse