Reelin Mobilizes a VAMP7-Dependent Synaptic Vesicle Pool and Selectively Augments Spontaneous Neurotransmission

Manjot Bal; Jeremy Leitz; Austin L. Reese; Denise M O Ramirez; Murat S Durakoglugil; Joachim Herz; Lisa M Monteggia; Ege T Kavalali

doi:10.1016/j.neuron.2013.08.024

Reelin Mobilizes a VAMP7-Dependent Synaptic Vesicle Pool and Selectively Augments Spontaneous Neurotransmission

Manjot Bal, Jeremy Leitz, Austin L. Reese, Denise M O Ramirez, Murat S Durakoglugil, Joachim Herz, Lisa M Monteggia, Ege T Kavalali

Research output: Contribution to journal › Article › peer-review

98 Scopus citations

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 Ca²⁺ initiatedvia ApoER2 signaling. The specificity of Reelin actionon spontaneous neurotransmitter release is encodedat 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 ofsynaptic vesicle-associated SNAREs and selectively augments action potential-independent neurotransmission

Original language	English (US)
Pages (from-to)	934-946
Number of pages	13
Journal	Neuron
Volume	80
Issue number	4
DOIs	https://doi.org/10.1016/j.neuron.2013.08.024
State	Published - Nov 20 2013

ASJC Scopus subject areas

General Neuroscience

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10.1016/j.neuron.2013.08.024

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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 Ca2+ initiatedvia ApoER2 signaling. The specificity of Reelin actionon spontaneous neurotransmitter release is encodedat 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 ofsynaptic vesicle-associated SNAREs and selectively augments action potential-independent neurotransmission",

author = "Manjot Bal and Jeremy Leitz and Reese, {Austin L.} and Ramirez, {Denise M O} and Durakoglugil, {Murat S} and Joachim Herz and Monteggia, {Lisa M} and Kavalali, {Ege T}",

note = "Funding Information: We thank Drs. Megumi Adachi, Elena Nosyreva, and Catherine Wasser for discussions and comments on the manuscript. We also thank Brent Trauterman for his excellent technical assistance. We are grateful to Drs. Mikhail Khvotchev and Yildirim Sara for their insight at early stages of this project. This work was supported by National Institutes of Health grants MH066198 (E.T.K.), NS075499 (E.T.K.), T32 NS069562 (J.L.), MH070727 (L.M.M.) and HL063762 (J.H.) as well as funding from the from the Brain & Behavior Research Foundation (L.M.M. and E.T.K.) and International Mental Health Research Organization (L.M.M.). ",

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AU - Leitz, Jeremy

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AU - Ramirez, Denise M O

AU - Durakoglugil, Murat S

AU - Herz, Joachim

AU - Monteggia, Lisa M

AU - Kavalali, Ege T

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PY - 2013/11/20

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N2 - 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 Ca2+ initiatedvia ApoER2 signaling. The specificity of Reelin actionon spontaneous neurotransmitter release is encodedat 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 ofsynaptic vesicle-associated SNAREs and selectively augments action potential-independent neurotransmission

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Reelin Mobilizes a VAMP7-Dependent Synaptic Vesicle Pool and Selectively Augments Spontaneous Neurotransmission

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