• Na-Ryum Bin, Mengjia Huang, and Shuzo Sugita.
• Division of Fundamental Neurobiology, Krembil Research Institute, University Health Network, Toronto, Ontario M5T 2S8, Canada; Department of Physiology, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
• Neuroscience. 2019 Nov 10; 420: 22-31.

AbstractTrafficking or delivery of neurotransmitter receptors on postsynaptic membranes is critical for basal neurotransmission and synaptic plasticity. Importantly, dysfunction of such postsynaptic receptor trafficking can lead to severe brain diseases such as Alzheimer's Disease, autism spectrum disorder, and intellectual disability, yet underlying mechanisms remain elusive. One attractive hypothesis is that postsynaptic SNARE proteins play key roles in the delivery of receptors by mediating membrane fusion at postsynaptic neurons. However, the identities of the critical SNARE proteins mediating the delivery remain controversial. The lack of consensus in previous studies is partly due to differences in preparations and methodologies. In this review, we propose to employ a pyramidal-neuron specific conditional knockout (cKO) model to study the roles of candidate SNARE proteins in postsynaptic receptor trafficking. We highlight our recent results which we obtained from such approaches to syntaxin-4 protein. These results provide clear evidence on the critical role of syntaxin-4 in trafficking of ionotropic glutamate receptors which are essential for basal neurotransmission, synaptic plasticity and spatial memory.Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

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