Investigating the Role of SNARE Proteins in Trafficking of Postsynaptic Receptors using Conditional Knockouts

Bin, Na-Ryum; Huang, Mengjia; Sugita, Shuzo

doi:10.1016/j.neuroscience.2018.11.027

Cited by 6 publications

(8 citation statements)

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“…Therefore, it appears that both syntaxin-3 and syntaxin-4 are potential t-SNAREs that mediate postsynaptic AMPAR delivery during LTP. Conversely, syntaxin-3 and syntaxin-4 KD had no effects on basal transmission, which suggests for the potential involvement of another syntaxin isoform in AMPAR delivery 11,14 .In a previous study, we utilized live murine models to examine the role of syntaxin-4 in postsynaptic neurons by generating a pyramidal neuron-specific conditional knockout (cKO) for syntaxin-4 15,16 . Analysis of syntaxin-4 cKO revealed significant decreases in basal synaptic transmission, LTP, surface expression of both AMPARs and NMDARs, and impaired spatial learning.…”

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confidence: 99%

“…Therefore, these data do not directly indicate a functional role of syntaxin-4 in AMPAR delivery during LTP and implicate a possible role of another syntaxin isoform, potentially syntaxin-3 in such processes 11 . In this aspect, it is important to analyze the role of syntaxin-3 in a similar manner to the previous analysis of syntaxin-4 15,16 . In this study, we generated syntaxin-3 cKO mice and performed electrophysiological and behavioral analyses to further examine the role of syntaxin-3 in postsynaptic basal neurotransmission, synaptic plasticity, learning and memory.…”

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confidence: 99%

“…In a previous study, we utilized live murine models to examine the role of syntaxin-4 in postsynaptic neurons by generating a pyramidal neuron-specific conditional knockout (cKO) for syntaxin-4 15,16 . Analysis of syntaxin-4 cKO revealed significant decreases in basal synaptic transmission, LTP, surface expression of both AMPARs and NMDARs, and impaired spatial learning.…”

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Syntaxin-3 is dispensable for basal neurotransmission and synaptic plasticity in postsynaptic hippocampal CA1 neurons

Shi

Harada

et al. 2020

Sci Rep

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Recent evidence suggests that SNARE fusion machinery play critical roles in postsynaptic neurotransmitter receptor trafficking, which is essential for synaptic plasticity. However, the key SNAREs involved remain highly controversial; syntaxin-3 and syntaxin-4 are leading candidates for the syntaxin isoform underlying postsynaptic plasticity. In a previous study, we showed that pyramidalneuron specific conditional knockout (cKO) of syntaxin-4 significantly reduces basal transmission, synaptic plasticity and impairs postsynaptic receptor trafficking. However, this does not exclude a role for syntaxin-3 in such processes. Here, we generated and analyzed syntaxin-3 cKO mice. Extracellular field recordings in hippocampal slices showed that syntaxin-3 cKO did not exhibit significant changes in CA1 basal neurotransmission or in paired-pulse ratios. Importantly, there were no observed differences during LTP in comparison to control mice. Syntaxin-3 cKO mice performed similarly as the controls in spatial and contextual learning tasks. Consistent with the minimal effects of syntaxin-3 cKO, syntaxin-3 mRNA level was very low in hippocampal and cortex pyramidal neurons, but strongly expressed in the corpus callosum and caudate axon fibers. Together, our data suggest that syntaxin-3 is dispensable for hippocampal basal neurotransmission and synaptic plasticity, and further supports the notion that syntaxin-4 is the major isoform mediating these processes.Synaptic transmission is essential for neuronal communication in the brain. During synaptic transmission, presynaptic neurons release neurotransmitters that bind to their respective receptors on the postsynaptic membrane. Ionotropic glutamate receptors (AMPARs and NMDARs) and GABA receptors on the postsynaptic membrane undergo receptor recycling. Receptor recycling is an essential process in synaptic plasticity such as long-term potentiation (LTP). LTP is a cellular correlate for higher-level cognitive functions of learning and memory 1-5 and requires rapid modifications in the quantity and composition of postsynaptic glutamate receptors 4,6,7 . Despite its importance, the underlying mechanisms of postsynaptic membrane receptor trafficking still remain unclear.Postsynaptic receptor trafficking employs a unique soluble NSF-attachment protein receptor (SNARE) complex that mediates the attachment and fusion of vesicles containing postsynaptic receptors to target membranes. The SNARE complex is composed of one vesicle membrane protein (v-SNARE; synaptobrevin) and two target membrane proteins (t-SNAREs; syntaxin and SNAP-25 isoforms) 8 . Botulinum neurotoxin B (BoNT/B) proteolyzes synaptobrevin-2 and when injected into CA1 pyramidal cells, blocks LTP induction 9 . This suggests that this open Scientific RepoRtS | (2020) 10:709 | https://doi.org/10.1038/s41598-019-57388-6www.nature.com/scientificreports www.nature.com/scientificreports/ v-SNARE is imperative for AMPAR delivery to the postsynaptic membrane during LTP. However, the particular isoforms of t-SNAREs involved in postsyna...

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Syntaxin-3 is dispensable for basal neurotransmission and synaptic plasticity in postsynaptic hippocampal CA1 neurons

Shi

Harada

et al. 2020

Sci Rep

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“…From the robust presence of syntaxin 4 and SNAP-25 throughout horizontal cell processes, it would be interesting to know if GABA release occurred extrasynaptically as well as synaptically from horizontal cells. Also, these SNARE proteins may function in the regulation of GABA or ionotropic glutamate receptor exocytosis, as syntaxin-4 is reported to be important for postsynaptic dendritic exocytosis in hippocampal neurons (Kennedy et al, 2010;Ovsepian and Dolly, 2011;Gu and Huganir, 2016;Bin et al, 2019).…”

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confidence: 99%

“…Immunoelectron microscopy places syntaxin-4 immunoreactivity in the lateral elements at photoreceptor synapses (Figures 6C,D). In other neuronal systems, syntaxin-4 is found in postsynaptic membranes and marks a domain for ionotropic glutamate receptor exocytosis in dendritic spines in hippocampus (Kennedy et al, 2010;Bin et al, 2019) and NGF release from Schwann cells (Lin et al, 2017). At the Drosophila neuromuscular junction, syntaxin-4 is postsynaptic and is involved in retrograde signaling to motoneurons (Harris et al, 2016) to regulate neurotransmitter release and the number of presynaptic active zones and Ca channels (Harris et al, 2018).…”

Section: Snare Proteinsmentioning

confidence: 99%

Vesicular Release of GABA by Mammalian Horizontal Cells Mediates Inhibitory Output to Photoreceptors

Hirano

Vuong

Kornmann

et al. 2020

Front. Cell. Neurosci.

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Feedback inhibition by horizontal cells regulates rod and cone photoreceptor calcium channels that control their release of the neurotransmitter glutamate. This inhibition contributes to synaptic gain control and the formation of the center-surround antagonistic receptive fields passed on to all downstream neurons, which is important for contrast sensitivity and color opponency in vision. In contrast to the plasmalemmal GABA transporter found in non-mammalian horizontal cells, there is evidence that the mechanism by which mammalian horizontal cells inhibit photoreceptors involves the vesicular release of the inhibitory neurotransmitter GABA. Historically, inconsistent findings of GABA and its biosynthetic enzyme, L-glutamate decarboxylase (GAD) in horizontal cells, and the apparent lack of surround response block by GABAergic agents diminished support for GABA's role in feedback inhibition. However, the immunolocalization of the vesicular GABA transporter (VGAT) in the dendritic and axonal endings of horizontal cells that innervate photoreceptor terminals suggested GABA was released via vesicular exocytosis. To test the idea that GABA is released from vesicles, we localized GABA and GAD, multiple SNARE complex proteins, synaptic vesicle proteins, and Cav channels that mediate exocytosis to horizontal cell dendritic tips and axonal terminals. To address the perceived relative paucity of synaptic vesicles in horizontal cell endings, we used conical electron tomography on mouse and guinea pig retinas that revealed small, clear-core vesicles, along with a few clathrin-coated vesicles and endosomes in horizontal cell processes within photoreceptor terminals. Some small-diameter vesicles were adjacent to the plasma membrane and plasma membrane specializations. To assess vesicular release, a functional assay involving incubation of retinal slices in luminal VGAT-C antibodies demonstrated vesicles fused with the membrane in a depolarization- and calcium-dependent manner, and these labeled vesicles can fuse multiple times. Finally, targeted elimination of VGAT in horizontal cells resulted in a loss of tonic, autaptic GABA currents, and of inhibitory feedback modulation of the cone photoreceptor Cai, consistent with the elimination of GABA release from horizontal cell endings. These results in mammalian retina identify the central role of vesicular release of GABA from horizontal cells in the feedback inhibition of photoreceptors.

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Neuronal SNAP-23 is critical for synaptic plasticity and spatial memory independently of NMDA receptor regulation

Huang¹,

Bin²,

Rai³

et al. 2023

iScience

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Investigating the Role of SNARE Proteins in Trafficking of Postsynaptic Receptors using Conditional Knockouts

Cited by 6 publications

References 50 publications

Syntaxin-3 is dispensable for basal neurotransmission and synaptic plasticity in postsynaptic hippocampal CA1 neurons

Syntaxin-3 is dispensable for basal neurotransmission and synaptic plasticity in postsynaptic hippocampal CA1 neurons

Vesicular Release of GABA by Mammalian Horizontal Cells Mediates Inhibitory Output to Photoreceptors

Neuronal SNAP-23 is critical for synaptic plasticity and spatial memory independently of NMDA receptor regulation

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