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SCAMP5 mediates activity-dependent enhancement of NHE6 recruitment to synaptic vesicles during synaptic plasticity

Lee, Unghwi, Ryu, Seung Hyun, Chang, Sunghoe·2021·Molecular Brain
DOI 10.1186/s13041-021-00763-0PMC PMC7934559
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Abstract

Na+(K+)/H+exchanger 6 (NHE6) on synaptic vesicle (SV) is critical for the presynaptic regulation of quantal size at the glutamatergic synapses by converting the chemical gradient (ΔpH) into membrane potential (Δψ) across the SV membrane. We recently found that NHE6 directly interacts with secretory carrier membrane protein 5 (SCAMP5), and SCAMP5-dependent recruitment of NHE6 to SVs controls the strength of synaptic transmission by modulation of quantal size of glutamate release at rest. It is, however, unknown whether NHE6 recruitment by SCAMP5 plays a role during synaptic plasticity. Here, we found that the number of NHE6-positive presynaptic boutons was significantly increased by the chemical long-term potentiation (cLTP). Since cLTP involves new synapse formation, our results indicated that NHE6 was recruited not only to the existing presynaptic boutons but also to the newly formed presynaptic boutons. Knock down of SCAMP5 completely abrogated the enhancement of NHE6 recruitment by cLTP. Interestingly, despite an increase in the number of NHE6-positive boutons by cLTP, the quantal size of glutamate release at the presynaptic terminals remained unaltered. Together with our recent results, our findings indicate that SCAMP5-dependent recruitment of NHE6 plays a critical role in manifesting presynaptic efficacy not only at rest but also during synaptic plasticity. Since both are autism candidate genes, reduced presynaptic efficacy by interfering with their interaction may underlie the molecular mechanism of synaptic dysfunction observed in autism.

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  • NHE6 is ubiquitously expressed in all cells of the body, but in the CNS it is highly expressed in neurons and to a lesser extent in glial cells.

    “NHE6 is ubiquitously expressed in all cells of the body, however, in the CNS it is highly expressed in neurons where abundant synaptic vesicles and neurotransmitter receptors recycle in synapses (Lee et al., 2020; Lee et al., 2021) and to a lesser extent in glial cells (Zhang et al., 2014).”

    From NHE6 depletion corrects ApoE4-mediated synaptic impairments and reduces amyloid plaque load (2021) · cites this paper as Lee et al., 2021

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Research works printed but not linked: 41

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Metadata

Authors
Lee, U., Ryu, S. H., & Chang, S.
ORCID
Chang, Sunghoe
Venue
Molecular Brain
Publisher
Springer Science and Business Media LLC
Published
2021-03-04
Volume
14
Issue
1
ISSN
1756-6606
DOI
10.1186/s13041-021-00763-0
PMC
PMC7934559
Cited by
12
References
4
Language
en
Licence
Funders
National Research Foundation of Korea (2019R1A2C2089182)

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