Inhibitors of synaptic vesicle exocytosis reduce surface expression of postsynaptic glutamate receptors

Abstract

Bafilomycin A1, a vacuolar H + -ATPase inhibitor, and botulinum toxin B and tetanus toxin, both vesicle fusion inhibitors, are widely known exocytosis blockers that have been used to inhibit the presynaptic release of neurotransmitters. However, protein trafficking mechanisms, such as the insertion of postsynaptic receptors and astrocytic glutamatereleasing channels into the plasma membrane, also require exocytosis. In our previous study, exocytosis inhibitors reduced the surface expression of astrocytic glutamate-releasing channels. Here, we further investigated whether exocytosis inhibitors influence the surface expression of postsynaptic receptors. Using pH-sensitive superecliptic pHluorin (SEP)-tagged postsynaptic glutamate receptors, including GluA1, GluA2, GluN1, and GluN2A, we found that bafilomycin A1, botulinum toxin B, and/or tetanus toxin reduce the SEP fluorescence of SEP-GluA1, SEP-GluA2, SEP-GluN1, and SEP-GluN2A. These findings indicate that presynaptic vesicle exocytosis inhibitors also affect the postsynaptic trafficking machinery for surface expression. Finally, this study provides profound insights assembling presynaptic, postsynaptic and astrocytic viewpoints into the interpretation of the data obtained using these synaptic vesicle exocytosis inhibitors.

Role of Rph3A in brain injury induced by experimental cerebral ischemia‐reperfusion model in rats

“…It has been shown that Rph3A expression at striatal synapses and its interaction with GluN2A‐containing NMDAR are increased in a rat model of Parkinson's disease 32 . GluN2A‐containing NMDARs translocate to the synapses due to the mobilization of pre‐assembled NMDARs from non‐synaptic pools 33 . However, the selective aggregation of these receptors is because Rph3A selectively binds to GluN2A, but not to other GluN2‐type regulatory NMDAR subunits.…”

“…GluN2A-containing NMDARs translocate to the synapses due to the mobilization of pre-assembled NMDARs from non-synaptic pools 33. However, the selective aggregation of these receptors is because Rph3A selectively binds to GluN2A, but not to other GluN2-type regulatory NMDAR subunits.…”

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“…The signals were detected using an Imagine ABI680 Analyzer (Amersham). Specific bands from western blots were quantified using ImageJ software and normalized against GAPDH as previously described (Woo et al 2020 ).…”