Distinct synaptic pools of DAPK1 differentially regulate activity-dependent synaptic CaMKII accumulation
Summary: The death-associated protein kinase 1 (DAPK1) regulates the synaptic movement of the Ca2+/calmodulin (CaM)-dependent protein kinase II (CaMKII). Synaptic CaMKII accumulation is mediated via binding to the NMDA-receptor subunit GluN2B and is required for long-term potentiation (LTP). By cont...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-05-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004223008003 |
| _version_ | 1797832679334346752 |
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| author | Jonathan E. Tullis K. Ulrich Bayer |
| author_facet | Jonathan E. Tullis K. Ulrich Bayer |
| author_sort | Jonathan E. Tullis |
| collection | DOAJ |
| description | Summary: The death-associated protein kinase 1 (DAPK1) regulates the synaptic movement of the Ca2+/calmodulin (CaM)-dependent protein kinase II (CaMKII). Synaptic CaMKII accumulation is mediated via binding to the NMDA-receptor subunit GluN2B and is required for long-term potentiation (LTP). By contrast, long-term depression (LTD) instead requires specific suppression of this movement, which is mediated by competitive DAPK1 binding to GluN2B. We find here that DAPK1 localizes to synapses via two distinct mechanisms: basal localization requires F-actin, but retention of DAPK1 at synapses during LTD requires an additional binding mode, likely to GluN2B. While F-actin binding mediates DAPK1 enrichment at synapses, it is not sufficient to suppress synaptic CaMKII movement. However, it is a prerequisite that enables the additional LTD-specific binding mode of DAPK1, which in turn mediates suppression of the CaMKII movement. Thus, both modes of synaptic DAPK1 localization work together to regulate synaptic CaMKII localization and thereby synaptic plasticity. |
| first_indexed | 2024-04-09T14:11:42Z |
| format | Article |
| id | doaj.art-2181192e239a48d4b8135d618406fe50 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-04-09T14:11:42Z |
| publishDate | 2023-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-2181192e239a48d4b8135d618406fe502023-05-06T04:38:45ZengElsevieriScience2589-00422023-05-01265106723Distinct synaptic pools of DAPK1 differentially regulate activity-dependent synaptic CaMKII accumulationJonathan E. Tullis0K. Ulrich Bayer1Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USADepartment of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Program in Neuroscience, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Corresponding authorSummary: The death-associated protein kinase 1 (DAPK1) regulates the synaptic movement of the Ca2+/calmodulin (CaM)-dependent protein kinase II (CaMKII). Synaptic CaMKII accumulation is mediated via binding to the NMDA-receptor subunit GluN2B and is required for long-term potentiation (LTP). By contrast, long-term depression (LTD) instead requires specific suppression of this movement, which is mediated by competitive DAPK1 binding to GluN2B. We find here that DAPK1 localizes to synapses via two distinct mechanisms: basal localization requires F-actin, but retention of DAPK1 at synapses during LTD requires an additional binding mode, likely to GluN2B. While F-actin binding mediates DAPK1 enrichment at synapses, it is not sufficient to suppress synaptic CaMKII movement. However, it is a prerequisite that enables the additional LTD-specific binding mode of DAPK1, which in turn mediates suppression of the CaMKII movement. Thus, both modes of synaptic DAPK1 localization work together to regulate synaptic CaMKII localization and thereby synaptic plasticity.http://www.sciencedirect.com/science/article/pii/S2589004223008003Molecular neuroscienceCellular neuroscience |
| spellingShingle | Jonathan E. Tullis K. Ulrich Bayer Distinct synaptic pools of DAPK1 differentially regulate activity-dependent synaptic CaMKII accumulation iScience Molecular neuroscience Cellular neuroscience |
| title | Distinct synaptic pools of DAPK1 differentially regulate activity-dependent synaptic CaMKII accumulation |
| title_full | Distinct synaptic pools of DAPK1 differentially regulate activity-dependent synaptic CaMKII accumulation |
| title_fullStr | Distinct synaptic pools of DAPK1 differentially regulate activity-dependent synaptic CaMKII accumulation |
| title_full_unstemmed | Distinct synaptic pools of DAPK1 differentially regulate activity-dependent synaptic CaMKII accumulation |
| title_short | Distinct synaptic pools of DAPK1 differentially regulate activity-dependent synaptic CaMKII accumulation |
| title_sort | distinct synaptic pools of dapk1 differentially regulate activity dependent synaptic camkii accumulation |
| topic | Molecular neuroscience Cellular neuroscience |
| url | http://www.sciencedirect.com/science/article/pii/S2589004223008003 |
| work_keys_str_mv | AT jonathanetullis distinctsynapticpoolsofdapk1differentiallyregulateactivitydependentsynapticcamkiiaccumulation AT kulrichbayer distinctsynapticpoolsofdapk1differentiallyregulateactivitydependentsynapticcamkiiaccumulation |