Locally-Induced CaMKII Translocation Requires Nucleotide Binding
Calcium-calmodulin-dependent protein kinase (CaMKII) is a molecule involved in several cell processes including plasticity related to learning and memory. Activation of NMDA-type glutamate receptors results in translocation of CaMKII to synapses. However, there are at least two distinct mechanisms b...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-02-01
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| Series: | Frontiers in Synaptic Neuroscience |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fnsyn.2020.00004/full |
| _version_ | 1828760477464788992 |
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| author | Zachary T. Fitzgerald Jacqueline K. Rose |
| author_facet | Zachary T. Fitzgerald Jacqueline K. Rose |
| author_sort | Zachary T. Fitzgerald |
| collection | DOAJ |
| description | Calcium-calmodulin-dependent protein kinase (CaMKII) is a molecule involved in several cell processes including plasticity related to learning and memory. Activation of NMDA-type glutamate receptors results in translocation of CaMKII to synapses. However, there are at least two distinct mechanisms by which glutamate-dependent CaMKII translocation occurs: one well-studied process resulting from whole-cell glutamate stimulation and one resulting from brief, local glutamate application. Unlike the relatively fast CaMKII translocation seen following whole-cell glutamate delivery (seconds), local application results in CaMKII translocation that occurs gradually within 6–10 min. This locally-induced translocation of CaMKII requires L-type Ca2+ channel co-activation but does not rely on GluN2B receptor subunit expression, unlike translocation following whole-cell application of glutamate. The current study examined if nucleotide binding is necessary for locally-induced CaMKII translocation, similar to CaMKII translocation resulting from whole-cell glutamate application. Three different mechanisms of inhibition were employed: staurosporine (ATP inhibitor), CaMKII(281–302) peptide inhibitor and expression of the K42M mutation. Locally-induced CaMKII translocation was moderately suppressed in the presence of either the broad-spectrum kinase inhibitor staurosporine (100 nm) or the CaMKII(281–302) peptide inhibitor. However, expression of the catalytically dead K42M mutation that prevents ATP-binding to CaMKII, significantly inhibited locally-induced translocation. Thus, CaMKII translocation following brief, local glutamate application requires nucleotide binding, providing support for future research into the molecular mechanisms of this distinct form of CaMKII translocation. |
| first_indexed | 2024-12-11T01:14:34Z |
| format | Article |
| id | doaj.art-61606307a1d04bd0bd4f62be10b8f3c6 |
| institution | Directory Open Access Journal |
| issn | 1663-3563 |
| language | English |
| last_indexed | 2024-12-11T01:14:34Z |
| publishDate | 2020-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Synaptic Neuroscience |
| spelling | doaj.art-61606307a1d04bd0bd4f62be10b8f3c62022-12-22T01:25:55ZengFrontiers Media S.A.Frontiers in Synaptic Neuroscience1663-35632020-02-011210.3389/fnsyn.2020.00004498768Locally-Induced CaMKII Translocation Requires Nucleotide BindingZachary T. FitzgeraldJacqueline K. RoseCalcium-calmodulin-dependent protein kinase (CaMKII) is a molecule involved in several cell processes including plasticity related to learning and memory. Activation of NMDA-type glutamate receptors results in translocation of CaMKII to synapses. However, there are at least two distinct mechanisms by which glutamate-dependent CaMKII translocation occurs: one well-studied process resulting from whole-cell glutamate stimulation and one resulting from brief, local glutamate application. Unlike the relatively fast CaMKII translocation seen following whole-cell glutamate delivery (seconds), local application results in CaMKII translocation that occurs gradually within 6–10 min. This locally-induced translocation of CaMKII requires L-type Ca2+ channel co-activation but does not rely on GluN2B receptor subunit expression, unlike translocation following whole-cell application of glutamate. The current study examined if nucleotide binding is necessary for locally-induced CaMKII translocation, similar to CaMKII translocation resulting from whole-cell glutamate application. Three different mechanisms of inhibition were employed: staurosporine (ATP inhibitor), CaMKII(281–302) peptide inhibitor and expression of the K42M mutation. Locally-induced CaMKII translocation was moderately suppressed in the presence of either the broad-spectrum kinase inhibitor staurosporine (100 nm) or the CaMKII(281–302) peptide inhibitor. However, expression of the catalytically dead K42M mutation that prevents ATP-binding to CaMKII, significantly inhibited locally-induced translocation. Thus, CaMKII translocation following brief, local glutamate application requires nucleotide binding, providing support for future research into the molecular mechanisms of this distinct form of CaMKII translocation.https://www.frontiersin.org/article/10.3389/fnsyn.2020.00004/fullCaMKIIATP—adenosine triphosphateglutamatesynapticcatalytic activitytranslocation |
| spellingShingle | Zachary T. Fitzgerald Jacqueline K. Rose Locally-Induced CaMKII Translocation Requires Nucleotide Binding Frontiers in Synaptic Neuroscience CaMKII ATP—adenosine triphosphate glutamate synaptic catalytic activity translocation |
| title | Locally-Induced CaMKII Translocation Requires Nucleotide Binding |
| title_full | Locally-Induced CaMKII Translocation Requires Nucleotide Binding |
| title_fullStr | Locally-Induced CaMKII Translocation Requires Nucleotide Binding |
| title_full_unstemmed | Locally-Induced CaMKII Translocation Requires Nucleotide Binding |
| title_short | Locally-Induced CaMKII Translocation Requires Nucleotide Binding |
| title_sort | locally induced camkii translocation requires nucleotide binding |
| topic | CaMKII ATP—adenosine triphosphate glutamate synaptic catalytic activity translocation |
| url | https://www.frontiersin.org/article/10.3389/fnsyn.2020.00004/full |
| work_keys_str_mv | AT zacharytfitzgerald locallyinducedcamkiitranslocationrequiresnucleotidebinding AT jacquelinekrose locallyinducedcamkiitranslocationrequiresnucleotidebinding |