AKAP18δ Anchors and Regulates CaMKII Activity at Phospholamban-SERCA2 and RYR
The sarcoplasmic reticulum (SR) Ca -ATPase 2 (SERCA2) mediates Ca reuptake into SR and thereby promotes cardiomyocyte relaxation, whereas the ryanodine receptor (RYR) mediates Ca release from SR and triggers contraction. Ca /CaMKII (CaM [calmodulin]-dependent protein kinase II) regulates activities...
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| Veröffentlicht in: | Circulation research 2022-01, Vol.130 (1), p.27-44 |
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| creator | Carlson, Cathrine R. Aronsen, Jan Magnus Bergan-Dahl, Anna Moutty, Marie Christine Lunde, Marianne Lunde, Per Kristian Jarstadmarken, Hilde Wanichawan, Pimthanya Pereira, Laetitia Kolstad, Terje R.S. Dalhus, Bjørn Subramanian, Hariharan Hille, Susanne Christensen, Geir Müller, Oliver J. Nikolaev, Viacheslav Bers, Donald M. Sjaastad, Ivar Shen, Xin Louch, William E. Klussmann, Enno Sejersted, Ole M. |
| description | The sarcoplasmic reticulum (SR) Ca
-ATPase 2 (SERCA2) mediates Ca
reuptake into SR and thereby promotes cardiomyocyte relaxation, whereas the ryanodine receptor (RYR) mediates Ca
release from SR and triggers contraction. Ca
/CaMKII (CaM [calmodulin]-dependent protein kinase II) regulates activities of SERCA2 through phosphorylation of PLN (phospholamban) and RYR through direct phosphorylation. However, the mechanisms for CaMKIIδ anchoring to SERCA2-PLN and RYR and its regulation by local Ca
signals remain elusive. The objective of this study was to investigate CaMKIIδ anchoring and regulation at SERCA2-PLN and RYR.
A role for AKAP18δ (A-kinase anchoring protein 18δ) in CaMKIIδ anchoring and regulation was analyzed by bioinformatics, peptide arrays, cell-permeant peptide technology, immunoprecipitations, pull downs, transfections, immunoblotting, proximity ligation, FRET-based CaMKII activity and ELISA-based assays, whole cell and SR vesicle fluorescence imaging, high-resolution microscopy, adenovirus transduction, adenoassociated virus injection, structural modeling, surface plasmon resonance, and alpha screen technology.
Our results show that AKAP18δ anchors and directly regulates CaMKIIδ activity at SERCA2-PLN and RYR, via 2 distinct AKAP18δ regions. An N-terminal region (AKAP18δ-N) inhibited CaMKIIδ through binding of a region homologous to the natural CaMKII inhibitor peptide and the Thr17-PLN region. AKAP18δ-N also bound CaM, introducing a second level of control. Conversely, AKAP18δ-C, which shares homology to neuronal CaMKIIα activator peptide (N2B-s), activated CaMKIIδ by lowering the apparent Ca
threshold for kinase activation and inducing CaM trapping. While AKAP18δ-C facilitated faster Ca
reuptake by SERCA2 and Ca
release through RYR, AKAP18δ-N had opposite effects. We propose a model where the 2 unique AKAP18δ regions fine-tune Ca
-frequency-dependent activation of CaMKIIδ at SERCA2-PLN and RYR.
AKAP18δ anchors and functionally regulates CaMKII activity at PLN-SERCA2 and RYR, indicating a crucial role of AKAP18δ in regulation of the heartbeat. To our knowledge, this is the first protein shown to enhance CaMKII activity in heart and also the first AKAP (A-kinase anchoring protein) reported to anchor a CaMKII isoform, defining AKAP18δ also as a CaM-KAP. |
| doi_str_mv | 10.1161/CIRCRESAHA.120.317976 |
| format | Article |
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-ATPase 2 (SERCA2) mediates Ca
reuptake into SR and thereby promotes cardiomyocyte relaxation, whereas the ryanodine receptor (RYR) mediates Ca
release from SR and triggers contraction. Ca
/CaMKII (CaM [calmodulin]-dependent protein kinase II) regulates activities of SERCA2 through phosphorylation of PLN (phospholamban) and RYR through direct phosphorylation. However, the mechanisms for CaMKIIδ anchoring to SERCA2-PLN and RYR and its regulation by local Ca
signals remain elusive. The objective of this study was to investigate CaMKIIδ anchoring and regulation at SERCA2-PLN and RYR.
A role for AKAP18δ (A-kinase anchoring protein 18δ) in CaMKIIδ anchoring and regulation was analyzed by bioinformatics, peptide arrays, cell-permeant peptide technology, immunoprecipitations, pull downs, transfections, immunoblotting, proximity ligation, FRET-based CaMKII activity and ELISA-based assays, whole cell and SR vesicle fluorescence imaging, high-resolution microscopy, adenovirus transduction, adenoassociated virus injection, structural modeling, surface plasmon resonance, and alpha screen technology.
Our results show that AKAP18δ anchors and directly regulates CaMKIIδ activity at SERCA2-PLN and RYR, via 2 distinct AKAP18δ regions. An N-terminal region (AKAP18δ-N) inhibited CaMKIIδ through binding of a region homologous to the natural CaMKII inhibitor peptide and the Thr17-PLN region. AKAP18δ-N also bound CaM, introducing a second level of control. Conversely, AKAP18δ-C, which shares homology to neuronal CaMKIIα activator peptide (N2B-s), activated CaMKIIδ by lowering the apparent Ca
threshold for kinase activation and inducing CaM trapping. While AKAP18δ-C facilitated faster Ca
reuptake by SERCA2 and Ca
release through RYR, AKAP18δ-N had opposite effects. We propose a model where the 2 unique AKAP18δ regions fine-tune Ca
-frequency-dependent activation of CaMKIIδ at SERCA2-PLN and RYR.
AKAP18δ anchors and functionally regulates CaMKII activity at PLN-SERCA2 and RYR, indicating a crucial role of AKAP18δ in regulation of the heartbeat. To our knowledge, this is the first protein shown to enhance CaMKII activity in heart and also the first AKAP (A-kinase anchoring protein) reported to anchor a CaMKII isoform, defining AKAP18δ also as a CaM-KAP.</description><identifier>ISSN: 0009-7330</identifier><identifier>EISSN: 1524-4571</identifier><identifier>DOI: 10.1161/CIRCRESAHA.120.317976</identifier><identifier>PMID: 34814703</identifier><language>eng</language><publisher>United States: Lippincott Williams & Wilkins</publisher><subject>Adaptor Proteins, Signal Transducing - chemistry ; Adaptor Proteins, Signal Transducing - metabolism ; Animals ; Binding Sites ; Calcium Signaling ; Calcium-Binding Proteins - metabolism ; Calcium-Calmodulin-Dependent Protein Kinase Type 2 - chemistry ; Calcium-Calmodulin-Dependent Protein Kinase Type 2 - metabolism ; Cells, Cultured ; HEK293 Cells ; Humans ; Life Sciences ; Myocytes, Cardiac - metabolism ; Protein Binding ; Rats ; Rats, Wistar ; Ryanodine Receptor Calcium Release Channel - metabolism ; Sarcoplasmic Reticulum Calcium-Transporting ATPases - metabolism</subject><ispartof>Circulation research, 2022-01, Vol.130 (1), p.27-44</ispartof><rights>Lippincott Williams & Wilkins</rights><rights>info:eu-repo/semantics/openAccess</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5146-cf68b7f9d5beede676f559200cbbc885afc392a1a080a2c9a552148702b7e85f3</citedby><cites>FETCH-LOGICAL-c5146-cf68b7f9d5beede676f559200cbbc885afc392a1a080a2c9a552148702b7e85f3</cites><orcidid>0000-0003-1145-596X ; 0000-0003-4004-5003 ; 0000-0002-2237-9483 ; 0000-0002-0511-6112 ; 0000-0002-9867-8391 ; 0000-0001-6360-3149 ; 0000-0002-7529-5179 ; 0000-0002-0589-5689 ; 0000-0001-8223-2638 ; 0000-0001-8817-3296</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,3674,26544,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34814703$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-04436022$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Carlson, Cathrine R.</creatorcontrib><creatorcontrib>Aronsen, Jan Magnus</creatorcontrib><creatorcontrib>Bergan-Dahl, Anna</creatorcontrib><creatorcontrib>Moutty, Marie Christine</creatorcontrib><creatorcontrib>Lunde, Marianne</creatorcontrib><creatorcontrib>Lunde, Per Kristian</creatorcontrib><creatorcontrib>Jarstadmarken, Hilde</creatorcontrib><creatorcontrib>Wanichawan, Pimthanya</creatorcontrib><creatorcontrib>Pereira, Laetitia</creatorcontrib><creatorcontrib>Kolstad, Terje R.S.</creatorcontrib><creatorcontrib>Dalhus, Bjørn</creatorcontrib><creatorcontrib>Subramanian, Hariharan</creatorcontrib><creatorcontrib>Hille, Susanne</creatorcontrib><creatorcontrib>Christensen, Geir</creatorcontrib><creatorcontrib>Müller, Oliver J.</creatorcontrib><creatorcontrib>Nikolaev, Viacheslav</creatorcontrib><creatorcontrib>Bers, Donald M.</creatorcontrib><creatorcontrib>Sjaastad, Ivar</creatorcontrib><creatorcontrib>Shen, Xin</creatorcontrib><creatorcontrib>Louch, William E.</creatorcontrib><creatorcontrib>Klussmann, Enno</creatorcontrib><creatorcontrib>Sejersted, Ole M.</creatorcontrib><title>AKAP18δ Anchors and Regulates CaMKII Activity at Phospholamban-SERCA2 and RYR</title><title>Circulation research</title><addtitle>Circ Res</addtitle><description>The sarcoplasmic reticulum (SR) Ca
-ATPase 2 (SERCA2) mediates Ca
reuptake into SR and thereby promotes cardiomyocyte relaxation, whereas the ryanodine receptor (RYR) mediates Ca
release from SR and triggers contraction. Ca
/CaMKII (CaM [calmodulin]-dependent protein kinase II) regulates activities of SERCA2 through phosphorylation of PLN (phospholamban) and RYR through direct phosphorylation. However, the mechanisms for CaMKIIδ anchoring to SERCA2-PLN and RYR and its regulation by local Ca
signals remain elusive. The objective of this study was to investigate CaMKIIδ anchoring and regulation at SERCA2-PLN and RYR.
A role for AKAP18δ (A-kinase anchoring protein 18δ) in CaMKIIδ anchoring and regulation was analyzed by bioinformatics, peptide arrays, cell-permeant peptide technology, immunoprecipitations, pull downs, transfections, immunoblotting, proximity ligation, FRET-based CaMKII activity and ELISA-based assays, whole cell and SR vesicle fluorescence imaging, high-resolution microscopy, adenovirus transduction, adenoassociated virus injection, structural modeling, surface plasmon resonance, and alpha screen technology.
Our results show that AKAP18δ anchors and directly regulates CaMKIIδ activity at SERCA2-PLN and RYR, via 2 distinct AKAP18δ regions. An N-terminal region (AKAP18δ-N) inhibited CaMKIIδ through binding of a region homologous to the natural CaMKII inhibitor peptide and the Thr17-PLN region. AKAP18δ-N also bound CaM, introducing a second level of control. Conversely, AKAP18δ-C, which shares homology to neuronal CaMKIIα activator peptide (N2B-s), activated CaMKIIδ by lowering the apparent Ca
threshold for kinase activation and inducing CaM trapping. While AKAP18δ-C facilitated faster Ca
reuptake by SERCA2 and Ca
release through RYR, AKAP18δ-N had opposite effects. We propose a model where the 2 unique AKAP18δ regions fine-tune Ca
-frequency-dependent activation of CaMKIIδ at SERCA2-PLN and RYR.
AKAP18δ anchors and functionally regulates CaMKII activity at PLN-SERCA2 and RYR, indicating a crucial role of AKAP18δ in regulation of the heartbeat. To our knowledge, this is the first protein shown to enhance CaMKII activity in heart and also the first AKAP (A-kinase anchoring protein) reported to anchor a CaMKII isoform, defining AKAP18δ also as a CaM-KAP.</description><subject>Adaptor Proteins, Signal Transducing - chemistry</subject><subject>Adaptor Proteins, Signal Transducing - metabolism</subject><subject>Animals</subject><subject>Binding Sites</subject><subject>Calcium Signaling</subject><subject>Calcium-Binding Proteins - metabolism</subject><subject>Calcium-Calmodulin-Dependent Protein Kinase Type 2 - chemistry</subject><subject>Calcium-Calmodulin-Dependent Protein Kinase Type 2 - metabolism</subject><subject>Cells, Cultured</subject><subject>HEK293 Cells</subject><subject>Humans</subject><subject>Life Sciences</subject><subject>Myocytes, Cardiac - metabolism</subject><subject>Protein Binding</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Ryanodine Receptor Calcium Release Channel - metabolism</subject><subject>Sarcoplasmic Reticulum Calcium-Transporting ATPases - metabolism</subject><issn>0009-7330</issn><issn>1524-4571</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>3HK</sourceid><recordid>eNpdkt1u1DAQhS0EotvCIwC5hIss4__4BimKlu6qC1QpXHBlOV6nCWTjxc5u1ffiOXgmskpbfq4sjb9zZkZnEHqBYY6xwG-LVVmUi6t8mc8xgTnFUknxCM0wJyxlXOLHaAYAKpWUwgk6jfEbAGaUqKfohLIMMwl0hj7mF_klzn79TPLeNj7ExPSbpHTX-84MLiaF-XCxWiW5HdpDO9wmZkguGx93je_MtjJ9erUoi5xMqq_lM_SkNl10z-_eM_Tl_eJzsUzXn85XRb5OLcdMpLYWWSVrteGVcxsnpKg5VwTAVpXNMm5qSxUx2EAGhlhlOCeYZRJIJV3Ga3qG3k2-u321dRvr-iGYTu9CuzXhVnvT6n9_-rbR1_6gFQdgKhsN3kwGzX-yZb7WxxowRgUQcsAj-2pibWjj0Pa698FoDBknWhEp2Ei8vhsn-B97Fwe9baN1XWd65_dREwFYKUYkGVF-b-ZjDK5-6I5BH5PVf5LVY7J6SnbUvfx74wfVfZQjwCbgxneDC_F7t79xQTfOdEOjx1MACpikZNwJMEhIjyVBfwN0zaw4</recordid><startdate>20220107</startdate><enddate>20220107</enddate><creator>Carlson, Cathrine R.</creator><creator>Aronsen, Jan Magnus</creator><creator>Bergan-Dahl, Anna</creator><creator>Moutty, Marie Christine</creator><creator>Lunde, Marianne</creator><creator>Lunde, Per Kristian</creator><creator>Jarstadmarken, Hilde</creator><creator>Wanichawan, Pimthanya</creator><creator>Pereira, Laetitia</creator><creator>Kolstad, Terje R.S.</creator><creator>Dalhus, Bjørn</creator><creator>Subramanian, Hariharan</creator><creator>Hille, Susanne</creator><creator>Christensen, Geir</creator><creator>Müller, Oliver J.</creator><creator>Nikolaev, Viacheslav</creator><creator>Bers, Donald M.</creator><creator>Sjaastad, Ivar</creator><creator>Shen, Xin</creator><creator>Louch, William E.</creator><creator>Klussmann, Enno</creator><creator>Sejersted, Ole M.</creator><general>Lippincott Williams & Wilkins</general><general>American Heart Association</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>3HK</scope><scope>1XC</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-1145-596X</orcidid><orcidid>https://orcid.org/0000-0003-4004-5003</orcidid><orcidid>https://orcid.org/0000-0002-2237-9483</orcidid><orcidid>https://orcid.org/0000-0002-0511-6112</orcidid><orcidid>https://orcid.org/0000-0002-9867-8391</orcidid><orcidid>https://orcid.org/0000-0001-6360-3149</orcidid><orcidid>https://orcid.org/0000-0002-7529-5179</orcidid><orcidid>https://orcid.org/0000-0002-0589-5689</orcidid><orcidid>https://orcid.org/0000-0001-8223-2638</orcidid><orcidid>https://orcid.org/0000-0001-8817-3296</orcidid></search><sort><creationdate>20220107</creationdate><title>AKAP18δ Anchors and Regulates CaMKII Activity at Phospholamban-SERCA2 and RYR</title><author>Carlson, Cathrine R. ; Aronsen, Jan Magnus ; Bergan-Dahl, Anna ; Moutty, Marie Christine ; Lunde, Marianne ; Lunde, Per Kristian ; Jarstadmarken, Hilde ; Wanichawan, Pimthanya ; Pereira, Laetitia ; Kolstad, Terje R.S. ; Dalhus, Bjørn ; Subramanian, Hariharan ; Hille, Susanne ; Christensen, Geir ; Müller, Oliver J. ; Nikolaev, Viacheslav ; Bers, Donald M. ; Sjaastad, Ivar ; Shen, Xin ; Louch, William E. ; Klussmann, Enno ; Sejersted, Ole M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5146-cf68b7f9d5beede676f559200cbbc885afc392a1a080a2c9a552148702b7e85f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Adaptor Proteins, Signal Transducing - chemistry</topic><topic>Adaptor Proteins, Signal Transducing - metabolism</topic><topic>Animals</topic><topic>Binding Sites</topic><topic>Calcium Signaling</topic><topic>Calcium-Binding Proteins - metabolism</topic><topic>Calcium-Calmodulin-Dependent Protein Kinase Type 2 - chemistry</topic><topic>Calcium-Calmodulin-Dependent Protein Kinase Type 2 - metabolism</topic><topic>Cells, Cultured</topic><topic>HEK293 Cells</topic><topic>Humans</topic><topic>Life Sciences</topic><topic>Myocytes, Cardiac - metabolism</topic><topic>Protein Binding</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Ryanodine Receptor Calcium Release Channel - metabolism</topic><topic>Sarcoplasmic Reticulum Calcium-Transporting ATPases - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Carlson, Cathrine R.</creatorcontrib><creatorcontrib>Aronsen, Jan Magnus</creatorcontrib><creatorcontrib>Bergan-Dahl, Anna</creatorcontrib><creatorcontrib>Moutty, Marie Christine</creatorcontrib><creatorcontrib>Lunde, Marianne</creatorcontrib><creatorcontrib>Lunde, Per Kristian</creatorcontrib><creatorcontrib>Jarstadmarken, Hilde</creatorcontrib><creatorcontrib>Wanichawan, Pimthanya</creatorcontrib><creatorcontrib>Pereira, Laetitia</creatorcontrib><creatorcontrib>Kolstad, Terje R.S.</creatorcontrib><creatorcontrib>Dalhus, Bjørn</creatorcontrib><creatorcontrib>Subramanian, Hariharan</creatorcontrib><creatorcontrib>Hille, Susanne</creatorcontrib><creatorcontrib>Christensen, Geir</creatorcontrib><creatorcontrib>Müller, Oliver J.</creatorcontrib><creatorcontrib>Nikolaev, Viacheslav</creatorcontrib><creatorcontrib>Bers, Donald M.</creatorcontrib><creatorcontrib>Sjaastad, Ivar</creatorcontrib><creatorcontrib>Shen, Xin</creatorcontrib><creatorcontrib>Louch, William E.</creatorcontrib><creatorcontrib>Klussmann, Enno</creatorcontrib><creatorcontrib>Sejersted, Ole M.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>NORA - Norwegian Open Research Archives</collection><collection>Hyper Article en Ligne (HAL)</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Circulation research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Carlson, Cathrine R.</au><au>Aronsen, Jan Magnus</au><au>Bergan-Dahl, Anna</au><au>Moutty, Marie Christine</au><au>Lunde, Marianne</au><au>Lunde, Per Kristian</au><au>Jarstadmarken, Hilde</au><au>Wanichawan, Pimthanya</au><au>Pereira, Laetitia</au><au>Kolstad, Terje R.S.</au><au>Dalhus, Bjørn</au><au>Subramanian, Hariharan</au><au>Hille, Susanne</au><au>Christensen, Geir</au><au>Müller, Oliver J.</au><au>Nikolaev, Viacheslav</au><au>Bers, Donald M.</au><au>Sjaastad, Ivar</au><au>Shen, Xin</au><au>Louch, William E.</au><au>Klussmann, Enno</au><au>Sejersted, Ole M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>AKAP18δ Anchors and Regulates CaMKII Activity at Phospholamban-SERCA2 and RYR</atitle><jtitle>Circulation research</jtitle><addtitle>Circ Res</addtitle><date>2022-01-07</date><risdate>2022</risdate><volume>130</volume><issue>1</issue><spage>27</spage><epage>44</epage><pages>27-44</pages><issn>0009-7330</issn><eissn>1524-4571</eissn><abstract>The sarcoplasmic reticulum (SR) Ca
-ATPase 2 (SERCA2) mediates Ca
reuptake into SR and thereby promotes cardiomyocyte relaxation, whereas the ryanodine receptor (RYR) mediates Ca
release from SR and triggers contraction. Ca
/CaMKII (CaM [calmodulin]-dependent protein kinase II) regulates activities of SERCA2 through phosphorylation of PLN (phospholamban) and RYR through direct phosphorylation. However, the mechanisms for CaMKIIδ anchoring to SERCA2-PLN and RYR and its regulation by local Ca
signals remain elusive. The objective of this study was to investigate CaMKIIδ anchoring and regulation at SERCA2-PLN and RYR.
A role for AKAP18δ (A-kinase anchoring protein 18δ) in CaMKIIδ anchoring and regulation was analyzed by bioinformatics, peptide arrays, cell-permeant peptide technology, immunoprecipitations, pull downs, transfections, immunoblotting, proximity ligation, FRET-based CaMKII activity and ELISA-based assays, whole cell and SR vesicle fluorescence imaging, high-resolution microscopy, adenovirus transduction, adenoassociated virus injection, structural modeling, surface plasmon resonance, and alpha screen technology.
Our results show that AKAP18δ anchors and directly regulates CaMKIIδ activity at SERCA2-PLN and RYR, via 2 distinct AKAP18δ regions. An N-terminal region (AKAP18δ-N) inhibited CaMKIIδ through binding of a region homologous to the natural CaMKII inhibitor peptide and the Thr17-PLN region. AKAP18δ-N also bound CaM, introducing a second level of control. Conversely, AKAP18δ-C, which shares homology to neuronal CaMKIIα activator peptide (N2B-s), activated CaMKIIδ by lowering the apparent Ca
threshold for kinase activation and inducing CaM trapping. While AKAP18δ-C facilitated faster Ca
reuptake by SERCA2 and Ca
release through RYR, AKAP18δ-N had opposite effects. We propose a model where the 2 unique AKAP18δ regions fine-tune Ca
-frequency-dependent activation of CaMKIIδ at SERCA2-PLN and RYR.
AKAP18δ anchors and functionally regulates CaMKII activity at PLN-SERCA2 and RYR, indicating a crucial role of AKAP18δ in regulation of the heartbeat. To our knowledge, this is the first protein shown to enhance CaMKII activity in heart and also the first AKAP (A-kinase anchoring protein) reported to anchor a CaMKII isoform, defining AKAP18δ also as a CaM-KAP.</abstract><cop>United States</cop><pub>Lippincott Williams & Wilkins</pub><pmid>34814703</pmid><doi>10.1161/CIRCRESAHA.120.317976</doi><tpages>18</tpages><orcidid>https://orcid.org/0000-0003-1145-596X</orcidid><orcidid>https://orcid.org/0000-0003-4004-5003</orcidid><orcidid>https://orcid.org/0000-0002-2237-9483</orcidid><orcidid>https://orcid.org/0000-0002-0511-6112</orcidid><orcidid>https://orcid.org/0000-0002-9867-8391</orcidid><orcidid>https://orcid.org/0000-0001-6360-3149</orcidid><orcidid>https://orcid.org/0000-0002-7529-5179</orcidid><orcidid>https://orcid.org/0000-0002-0589-5689</orcidid><orcidid>https://orcid.org/0000-0001-8223-2638</orcidid><orcidid>https://orcid.org/0000-0001-8817-3296</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0009-7330 |
| ispartof | Circulation research, 2022-01, Vol.130 (1), p.27-44 |
| issn | 0009-7330 1524-4571 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_9500498 |
| source | Journals@Ovid Ovid Autoload; MEDLINE; NORA - Norwegian Open Research Archives; American Heart Association Journals; EZB-FREE-00999 freely available EZB journals |
| subjects | Adaptor Proteins, Signal Transducing - chemistry Adaptor Proteins, Signal Transducing - metabolism Animals Binding Sites Calcium Signaling Calcium-Binding Proteins - metabolism Calcium-Calmodulin-Dependent Protein Kinase Type 2 - chemistry Calcium-Calmodulin-Dependent Protein Kinase Type 2 - metabolism Cells, Cultured HEK293 Cells Humans Life Sciences Myocytes, Cardiac - metabolism Protein Binding Rats Rats, Wistar Ryanodine Receptor Calcium Release Channel - metabolism Sarcoplasmic Reticulum Calcium-Transporting ATPases - metabolism |
| title | AKAP18δ Anchors and Regulates CaMKII Activity at Phospholamban-SERCA2 and RYR |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-08T13%3A28%3A37IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=AKAP18%CE%B4%20Anchors%20and%20Regulates%20CaMKII%20Activity%20at%20Phospholamban-SERCA2%20and%20RYR&rft.jtitle=Circulation%20research&rft.au=Carlson,%20Cathrine%20R.&rft.date=2022-01-07&rft.volume=130&rft.issue=1&rft.spage=27&rft.epage=44&rft.pages=27-44&rft.issn=0009-7330&rft.eissn=1524-4571&rft_id=info:doi/10.1161/CIRCRESAHA.120.317976&rft_dat=%3Cproquest_pubme%3E2601994272%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2601994272&rft_id=info:pmid/34814703&rfr_iscdi=true |