Ca2+-PP2B-PSD-95 axis: A novel regulatory mechanism of the phosphorylation state of Serine 295 of PSD-95.

The phosphorylation state of PSD-95 at Serine 295 (Ser295) is important for the regulation of synaptic plasticity. Although the activation of NMDA receptors (NMDARs), which initiates an intracellular calcium signaling cascade, decreases phosphorylated Ser295 (pS295) of PSD-95, the molecular mechanis...

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Main Authors: Takahiko Chimura, Toshiya Manabe
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2024-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0313441
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author Takahiko Chimura
Toshiya Manabe
author_facet Takahiko Chimura
Toshiya Manabe
author_sort Takahiko Chimura
collection DOAJ
description The phosphorylation state of PSD-95 at Serine 295 (Ser295) is important for the regulation of synaptic plasticity. Although the activation of NMDA receptors (NMDARs), which initiates an intracellular calcium signaling cascade, decreases phosphorylated Ser295 (pS295) of PSD-95, the molecular mechanisms are not fully understood. We found that the calcium-activated protein phosphatase PP2B dephosphorylated pS295 not only in basal conditions but also in NMDAR-activated conditions in cultured neurons. The biochemical assay also revealed the dephosphorylation of pS295 by PP2B, consistently supporting the results obtained using neurons. The newly identified calcium signaling cascade "Ca2+-PP2B-PSD-95 axis" would play an important role in the molecular mechanism for NMDA receptor-dependent plasticity.
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publisher Public Library of Science (PLoS)
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spelling doaj-art-c176a44f1cb7459699ba145d1a42e3f02025-08-20T02:58:11ZengPublic Library of Science (PLoS)PLoS ONE1932-62032024-01-011911e031344110.1371/journal.pone.0313441Ca2+-PP2B-PSD-95 axis: A novel regulatory mechanism of the phosphorylation state of Serine 295 of PSD-95.Takahiko ChimuraToshiya ManabeThe phosphorylation state of PSD-95 at Serine 295 (Ser295) is important for the regulation of synaptic plasticity. Although the activation of NMDA receptors (NMDARs), which initiates an intracellular calcium signaling cascade, decreases phosphorylated Ser295 (pS295) of PSD-95, the molecular mechanisms are not fully understood. We found that the calcium-activated protein phosphatase PP2B dephosphorylated pS295 not only in basal conditions but also in NMDAR-activated conditions in cultured neurons. The biochemical assay also revealed the dephosphorylation of pS295 by PP2B, consistently supporting the results obtained using neurons. The newly identified calcium signaling cascade "Ca2+-PP2B-PSD-95 axis" would play an important role in the molecular mechanism for NMDA receptor-dependent plasticity.https://doi.org/10.1371/journal.pone.0313441
spellingShingle Takahiko Chimura
Toshiya Manabe
Ca2+-PP2B-PSD-95 axis: A novel regulatory mechanism of the phosphorylation state of Serine 295 of PSD-95.
PLoS ONE
title Ca2+-PP2B-PSD-95 axis: A novel regulatory mechanism of the phosphorylation state of Serine 295 of PSD-95.
title_full Ca2+-PP2B-PSD-95 axis: A novel regulatory mechanism of the phosphorylation state of Serine 295 of PSD-95.
title_fullStr Ca2+-PP2B-PSD-95 axis: A novel regulatory mechanism of the phosphorylation state of Serine 295 of PSD-95.
title_full_unstemmed Ca2+-PP2B-PSD-95 axis: A novel regulatory mechanism of the phosphorylation state of Serine 295 of PSD-95.
title_short Ca2+-PP2B-PSD-95 axis: A novel regulatory mechanism of the phosphorylation state of Serine 295 of PSD-95.
title_sort ca2 pp2b psd 95 axis a novel regulatory mechanism of the phosphorylation state of serine 295 of psd 95
url https://doi.org/10.1371/journal.pone.0313441
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