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Ca2+/Calmodulin Binding to PSD-95 Downregulates Its Palmitoylation and AMPARs in Long-Term Depression.

ABSTRACT: AMPA-type glutamate receptors (AMPARs) are clustered into functional nanodomains at postsynaptic sites through anchorage by the scaffolding protein, postsynaptic density protein-95 (PSD-95). The synaptic abundance of AMPARs is dynamically controlled in various forms of synaptic plasticity. Removal of AMPARs from the synapse in long-term depression (LTD) requires mobilization of PSD-95 away from the synapse. The molecular mechanisms underlying PSD-95 dispersal from the synapse during LTD are not completely understood. Here we show that, following Ca2+ influx, binding of Ca2+/calmodulin (CaM) to PSD-95 triggers loss of synaptic PSD-95 as well as surface AMPARs during chemically induced LTD in cultured rat neurons. Our data suggest that a reduction in PSD-95 palmitoylation mediates the effect of Ca2+/CaM on PSD-95 synaptic levels during LTD. These findings reveal a novel molecular mechanism for synaptic AMPAR regulation in LTD.

SUBMITTER: Chowdhury D

PROVIDER: S-EPMC6422948 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Ca<sup>2+</sup>/Calmodulin Binding to PSD-95 Downregulates Its Palmitoylation and AMPARs in Long-Term Depression.

Chowdhury Dhrubajyoti D Hell Johannes W JW

Frontiers in synaptic neuroscience 20190312

AMPA-type glutamate receptors (AMPARs) are clustered into functional nanodomains at postsynaptic sites through anchorage by the scaffolding protein, postsynaptic density protein-95 (PSD-95). The synaptic abundance of AMPARs is dynamically controlled in various forms of synaptic plasticity. Removal of AMPARs from the synapse in long-term depression (LTD) requires mobilization of PSD-95 away from the synapse. The molecular mechanisms underlying PSD-95 dispersal from the synapse during LTD are not ...[more]

PMID: 30914943

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