NMDA receptor subunit composition controls dendritogenesis of hippocampal neurons through CAMKII, CREB-P, and H3K27ac.

Dendrite arbor growth, or dendritogenesis, is choreographed by a diverse set of cues, including the NMDA receptor (NMDAR) subunits NR2A and NR2B. While NR1NR2B receptors are predominantly expressed in immature neurons and promote plasticity, NR1NR2A receptors are mainly expressed in mature neurons a...

Descripción completa

Detalles Bibliográficos
Autores: Bustos, Fernando J, Jury, Nur, Martínez, Pablo, Ampuero, Estívaliz, Campos, Matias, Abarzúa, Sebastián, Jaramillo, Karen, Ibing, Susane, Mardones, Muriel D., Haensgen, Henny, Kzhyshkowska, Julia, Tevy, María Florencia, Neve, Rachael, Sanhueza, Magdalena, Varela-Nallar, Lorena, Montecino, Martín, Van Zundert, Brigitte
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2017
País:Chile
OAI Identifier:oai:repositorio.anid.cl:10533/236606
Acceso en línea:https://hdl.handle.net/10533/236606
Access Level:acceso abierto
id CL_7230eb9315d10bd48bde6896ba4e080c
oai_identifier_str oai:repositorio.anid.cl:10533/236606
network_acronym_str CL
network_name_str Chile
repository_id_str
dc.title.es_CL.fl_str_mv NMDA receptor subunit composition controls dendritogenesis of hippocampal neurons through CAMKII, CREB-P, and H3K27ac.
title NMDA receptor subunit composition controls dendritogenesis of hippocampal neurons through CAMKII, CREB-P, and H3K27ac.
spellingShingle NMDA receptor subunit composition controls dendritogenesis of hippocampal neurons through CAMKII, CREB-P, and H3K27ac.
Bustos, Fernando J
title_short NMDA receptor subunit composition controls dendritogenesis of hippocampal neurons through CAMKII, CREB-P, and H3K27ac.
title_full NMDA receptor subunit composition controls dendritogenesis of hippocampal neurons through CAMKII, CREB-P, and H3K27ac.
title_fullStr NMDA receptor subunit composition controls dendritogenesis of hippocampal neurons through CAMKII, CREB-P, and H3K27ac.
title_full_unstemmed NMDA receptor subunit composition controls dendritogenesis of hippocampal neurons through CAMKII, CREB-P, and H3K27ac.
title_sort NMDA receptor subunit composition controls dendritogenesis of hippocampal neurons through CAMKII, CREB-P, and H3K27ac.
dc.creator.none.fl_str_mv Bustos, Fernando J
Jury, Nur
Martínez, Pablo
Ampuero, Estívaliz
Campos, Matias
Abarzúa, Sebastián
Jaramillo, Karen
Ibing, Susane
Mardones, Muriel D.
Haensgen, Henny
Kzhyshkowska, Julia
Tevy, María Florencia
Neve, Rachael
Sanhueza, Magdalena
Varela-Nallar, Lorena
Montecino, Martín
Van Zundert, Brigitte
author Bustos, Fernando J
author_facet Bustos, Fernando J
Jury, Nur
Martínez, Pablo
Ampuero, Estívaliz
Campos, Matias
Abarzúa, Sebastián
Jaramillo, Karen
Ibing, Susane
Mardones, Muriel D.
Haensgen, Henny
Kzhyshkowska, Julia
Tevy, María Florencia
Neve, Rachael
Sanhueza, Magdalena
Varela-Nallar, Lorena
Montecino, Martín
Van Zundert, Brigitte
author_role author
author2 Jury, Nur
Martínez, Pablo
Ampuero, Estívaliz
Campos, Matias
Abarzúa, Sebastián
Jaramillo, Karen
Ibing, Susane
Mardones, Muriel D.
Haensgen, Henny
Kzhyshkowska, Julia
Tevy, María Florencia
Neve, Rachael
Sanhueza, Magdalena
Varela-Nallar, Lorena
Montecino, Martín
Van Zundert, Brigitte
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
description Dendrite arbor growth, or dendritogenesis, is choreographed by a diverse set of cues, including the NMDA receptor (NMDAR) subunits NR2A and NR2B. While NR1NR2B receptors are predominantly expressed in immature neurons and promote plasticity, NR1NR2A receptors are mainly expressed in mature neurons and induce circuit stability. How the different subunits regulate these processes is unclear, but this is likely related to the presence of their distinct C-terminal sequences that couple different signaling proteins. Calcium-calmodulin-dependent protein kinase II (CaMKII) is an interesting candidate as this protein can be activated by calcium influx through NMDARs. CaMKII triggers a series of biochemical signaling cascades, involving the phosphorylation of diverse targets. Among them, the activation of cAMP response element-binding protein (CREB-P) pathway triggers a plasticity-specific transcriptional program through unknown epigenetic mechanisms. Here, we found that dendritogenesis in hippocampal neurons is impaired by several well-characterized constructs (i.e., NR2B-RS/QD) and peptides (i.e., tatCN21) that specifically interfere with the recruitment and interaction of CaMKII with the NR2B C-terminal domain. Interestingly, we found that transduction of NR2AΔIN, a mutant NR2A construct with increased interaction to CaMKII, reactivates dendritogenesis in mature hippocampal neurons in vitro and in vivo. To gain insights into the signaling and epigenetic mechanisms underlying NMDAR-mediated dendritogenesis, we used immunofluorescence staining to detect CREB-P and acetylated lysine 27 of histone H3 (H3K27ac), an activation-associated histone tail mark. In contrast to control mature neurons, our data shows that activation of the NMDAR/CaMKII/ERK-P/CREB-P signaling axis in neurons expressing NR2AΔIN is not correlated with increased nuclear H3K27ac levels.
publishDate 2017
dc.date.issued.es_CL.fl_str_mv 2017
dc.date.accessioned.none.fl_str_mv 2019-11-08T13:40:23Z
2022-07-07T21:55:03Z
dc.date.available.none.fl_str_mv 2019-11-08T13:40:23Z
2022-07-07T21:55:03Z
dc.type.none.fl_str_mv Articulo
dc.type.driver.none.fl_str_mv info:eu-repo/semantics/article
dc.type.openaire.none.fl_str_mv info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.folio.es_CL.fl_str_mv 21151265
dc.identifier.folio.none.fl_str_mv 21151265
dc.identifier.uri.none.fl_str_mv https://hdl.handle.net/10533/236606
identifier_str_mv 21151265
url https://hdl.handle.net/10533/236606
dc.relation.none.fl_str_mv instname: Conicyt
reponame: Repositorio Digital RI2.0
dc.relation.projectid.es_CL.fl_str_mv info:eu-repo/grantAgreement//21151265
dc.relation.set.none.fl_str_mv info:eu-repo/semantics/dataset/hdl.handle.net/10533/93477
dc.relation.uri.es_CL.fl_str_mv https://www.ncbi.nlm.nih.gov/pubmed/28160495
dc.rights.es_CL.fl_str_mv info:eu-repo/semantics/openAccess
dc.rights.*.fl_str_mv Attribution-NonCommercial-NoDerivs 3.0 Chile
dc.rights.uri.*.fl_str_mv http://creativecommons.org/licenses/by-nc-nd/3.0/cl/
eu_rights_str_mv openAccess
rights_invalid_str_mv Attribution-NonCommercial-NoDerivs 3.0 Chile
http://creativecommons.org/licenses/by-nc-nd/3.0/cl/
bitstream.url.fl_str_mv https://repositorio.anid.cl/bitstreams/0c4a07ab-9ba7-4661-9a5d-351455a3794d/download
https://repositorio.anid.cl/bitstreams/0fccefe8-f188-4e9c-bf15-293b89c7023c/download
https://repositorio.anid.cl/bitstreams/39835f40-bac1-416d-bea2-68e039c72b2b/download
https://repositorio.anid.cl/bitstreams/c5ac20af-970e-477c-8ee7-898144bbc390/download
https://repositorio.anid.cl/bitstreams/10e1b6f2-b501-4c80-b2c4-3a87ee055c8a/download
bitstream.checksum.fl_str_mv e1fe69fd932eca1539a5131ad727d3f9
593a6e7305c66c56041a9f9e15a649c1
f97bcfdf58f3e17b5cec231112dab5b1
ee19e583d7c82998b368572901c9a28d
e2d91a1e2d48e544b248b7b67493ab79
bitstream.checksumAlgorithm.fl_str_mv MD5
MD5
MD5
MD5
MD5
repository.name.fl_str_mv Repositorio ANID
repository.mail.fl_str_mv aletelier@anid.cl
_version_ 1843518673705238528
spelling Van Zundert, BrigitteMontecino, MartínVarela-Nallar, LorenaSanhueza, MagdalenaNeve, RachaelTevy, María FlorenciaKzhyshkowska, JuliaHaensgen, HennyMardones, Muriel D.Ibing, SusaneJaramillo, KarenAbarzúa, SebastiánCampos, MatiasAmpuero, EstívalizMartínez, PabloJury, NurBustos, Fernando J2017https://hdl.handle.net/10533/236606http://purl.org/coar/access_right/c_abf2NMDA receptor subunit composition controls dendritogenesis of hippocampal neurons through CAMKII, CREB-P, and H3K27ac.Bustos, Fernando JJury, NurMartínez, PabloAmpuero, EstívalizCampos, MatiasAbarzúa, SebastiánJaramillo, KarenIbing, SusaneMardones, Muriel D.Haensgen, HennyKzhyshkowska, JuliaTevy, María FlorenciaNeve, RachaelSanhueza, MagdalenaVarela-Nallar, LorenaMontecino, MartínVan Zundert, Brigitte2019-11-08T13:40:23Z2022-07-07T21:55:03Z2019-11-08T13:40:23Z2022-07-07T21:55:03Z2017Dendrite arbor growth, or dendritogenesis, is choreographed by a diverse set of cues, including the NMDA receptor (NMDAR) subunits NR2A and NR2B. While NR1NR2B receptors are predominantly expressed in immature neurons and promote plasticity, NR1NR2A receptors are mainly expressed in mature neurons and induce circuit stability. How the different subunits regulate these processes is unclear, but this is likely related to the presence of their distinct C-terminal sequences that couple different signaling proteins. Calcium-calmodulin-dependent protein kinase II (CaMKII) is an interesting candidate as this protein can be activated by calcium influx through NMDARs. CaMKII triggers a series of biochemical signaling cascades, involving the phosphorylation of diverse targets. Among them, the activation of cAMP response element-binding protein (CREB-P) pathway triggers a plasticity-specific transcriptional program through unknown epigenetic mechanisms. Here, we found that dendritogenesis in hippocampal neurons is impaired by several well-characterized constructs (i.e., NR2B-RS/QD) and peptides (i.e., tatCN21) that specifically interfere with the recruitment and interaction of CaMKII with the NR2B C-terminal domain. Interestingly, we found that transduction of NR2AΔIN, a mutant NR2A construct with increased interaction to CaMKII, reactivates dendritogenesis in mature hippocampal neurons in vitro and in vivo. To gain insights into the signaling and epigenetic mechanisms underlying NMDAR-mediated dendritogenesis, we used immunofluorescence staining to detect CREB-P and acetylated lysine 27 of histone H3 (H3K27ac), an activation-associated histone tail mark. In contrast to control mature neurons, our data shows that activation of the NMDAR/CaMKII/ERK-P/CREB-P signaling axis in neurons expressing NR2AΔIN is not correlated with increased nuclear H3K27ac levels.2115126521151265virtual::46274-1https://hdl.handle.net/10533/236606instname: Conicytreponame: Repositorio Digital RI2.0info:eu-repo/grantAgreement//21151265info:eu-repo/semantics/dataset/hdl.handle.net/10533/93477https://www.ncbi.nlm.nih.gov/pubmed/28160495info:eu-repo/semantics/openAccessAttribution-NonCommercial-NoDerivs 3.0 Chilehttp://creativecommons.org/licenses/by-nc-nd/3.0/cl/NMDA receptor subunit composition controls dendritogenesis of hippocampal neurons through CAMKII, CREB-P, and H3K27ac.Articuloinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionArticulohttps://hdl.handle.net/10533/236606http://purl.org/coar/resource_type/c_2df8fbb165b1c099-a734-4bea-addc-58ef429247c8virtual::46274-165b1c099-a734-4bea-addc-58ef429247c8virtual::46274-1ORIGINAL(2017) Bustos FJ. NMDA dendritogenesis CAMKII, CREB, H3K27ac.pdfapplication/pdf3996366https://repositorio.anid.cl/bitstreams/0c4a07ab-9ba7-4661-9a5d-351455a3794d/downloade1fe69fd932eca1539a5131ad727d3f9MD51LICENSElicense.txttext/plain1779https://repositorio.anid.cl/bitstreams/0fccefe8-f188-4e9c-bf15-293b89c7023c/download593a6e7305c66c56041a9f9e15a649c1MD52CC-LICENSElicense_rdfapplication/octet-stream1232https://repositorio.anid.cl/bitstreams/39835f40-bac1-416d-bea2-68e039c72b2b/downloadf97bcfdf58f3e17b5cec231112dab5b1MD53TEXT(2017) Bustos FJ. NMDA dendritogenesis CAMKII, CREB, H3K27ac.pdf.txtExtracted texttext/plain82086https://repositorio.anid.cl/bitstreams/c5ac20af-970e-477c-8ee7-898144bbc390/downloadee19e583d7c82998b368572901c9a28dMD54THUMBNAIL(2017) Bustos FJ. NMDA dendritogenesis CAMKII, CREB, H3K27ac.pdf.jpgIM Thumbnailimage/jpeg6454https://repositorio.anid.cl/bitstreams/10e1b6f2-b501-4c80-b2c4-3a87ee055c8a/downloade2d91a1e2d48e544b248b7b67493ab79MD5510533/236606oai:repositorio.anid.cl:10533/2366062023-07-24 17:59:43.127http://creativecommons.org/licenses/by-nc-nd/3.0/cl/info:eu-repo/semantics/openAccesshttps://repositorio.anid.clRepositorio ANIDaletelier@anid.clTGljZW5jaWEgZGUgRGlzdHJpYnVjacOzbiBObyBFeGNsdXNpdmEKCkFsIGZpcm1hciB5IHByZXNlbnRhciBlc3RhIGxpY2VuY2lhICwgdXN0ZWQgKGVsIGF1dG9yKGVzKSBvIHRpdHVsYXIgZGUgZGVyZWNob3MgZGUgYXV0b3IpIGdhcmFudGl6YSBhIGxhIENvbWlzacOzbiBOYWNpb25hbCBkZSBJbnZlc3RpZ2FjacOzbiBDaWVudMOtdGljYSB5IFRlY25vbMOzZ2ljYSAoQ09OSUNZVCkgZWwgZGVyZWNobyBubyBleGNsdXNpdm8gZGUgcmVwcm9kdWNpciAsIHRyYWR1Y2lyIChjb21vIHNlIGRlZmluZSBtw6FzIGFiYWpvKSAsIHkvbyBkaXN0cmlidWlyIHN1IGRvY3VtZW50byAoaW5jbHV5ZW5kbyBlbCByZXN1bWVuKSBlbiB0b2RvIGVsIG11bmRvIGVuIGZvcm1hIGltcHJlc2EgeSBlbiBmb3JtYXRvIGVsZWN0csOzbmljbyB5IGVuIGN1YWxxdWllciBtZWRpbywgaW5jbHV5ZW5kbywgcGVybyBubyBsaW1pdGFkbyBhLCBhdWRpbyBvIHbDrWRlby4KClVzdGVkIGFjZXB0YSBxdWUgQ09OSUNZVCBwdWVkZSwgc2luIGFsdGVyYXIgc3UgY29udGVuaWRvLCBjb252ZXJ0aXJsbyBhIGN1YWxxdWllciBtZWRpbyBvIGZvcm1hdG8gcGFyYSBlbCBmaW4gZGUgbGEgY29uc2VydmFjacOzbi4KClRhbWJpw6luIGFjZXB0YSBxdWUgQ09OSUNZVCBwdWVkZSB0ZW5lciBtw6FzIGRlIHVuYSBjb3BpYSBkZSBlc3RlIGRvY3VtZW50byBwYXJhIGZpbmVzIGRlIHNlZ3VyaWRhZCwgY29waWFzIGRlIHNlZ3VyaWRhZCB5IGNvbnNlcnZhY2nDs24uCgpVc3RlZCBkZWNsYXJhIHF1ZSBlbCBkb2N1bWVudG8gZXMgdW4gdHJhYmFqbyBvcmlnaW5hbCwgeSBxdWUgdXN0ZWQgdGllbmUgZWwgZGVyZWNobyBkZSBvdG9yZ2FyIGxvcyBkZXJlY2hvcyBjb250ZW5pZG9zIGVuIGVzdGEgbGljZW5jaWEuIFRhbWJpw6luIGRlY2xhcmEgcXVlIHN1IHBldGljacOzbiBubywgYSBsbyBtZWpvciBkZSBzdSBjb25vY2ltaWVudG8sIGluZnJpbmdlIGxvcyBkZXJlY2hvcyBkZSBhdXRvciBkZSBuYWRpZS4KClNpIGVsIGRvY3VtZW50byBjb250aWVuZSBtYXRlcmlhbGVzIGRlIGxvcyBxdWUgbm8gdGllbmVuIGRlcmVjaG9zIGRlIGF1dG9yICwgdXN0ZWQgZGVjbGFyYSBxdWUgaGEgb2J0ZW5pZG8gZWwgcGVybWlzbyBzaW4gcmVzdHJpY2Npw7NuIGRlbCBwcm9waWV0YXJpbyBkZSBsb3MgZGVyZWNob3MgcmVxdWVyaWRvcyBwb3IgZXN0YSBsaWNlbmNpYSB5IHF1ZSBlc2UgbWF0ZXJpYWwgY3V5b3MgZGVyZWNob3Mgc29uIGRlIHRlcmNlcm9zIGVzdMOhIGNsYXJhbWVudGUgaWRlbnRpZmljYWRvIHkgcmVjb25vY2lkbyBlbiBlbCB0ZXh0byBvIGNvbnRlbmlkbyBkZWwgZG9jdW1lbnRvIGVudHJlZ2Fkby4KClNJIEVMIEVOVsONTyBTRSBCQVNBIEVOIEVMIFRSQUJBSk8gUVVFIEhBIFNJRE8gUEFUUk9OQURPIE8gQVBPWUFETyBQT1IgQUxHVU5BIElOU1RJVFVDScOTTiBRVUUgTk8gU0VBIENPTklDWVQsIFVTVEVEIEFDRVBUQSBRVUUgSEEgQ1VNUExJRE8gQSBDVUFMUVVJRVIgREVSRUNITyBERSBSRVZJU0nDk04gVSBPVFJBUyBPQkxJR0FDSU9ORVMgUkVRVUVSSURBUyBQT1IgRElDSE8gQ09OVFJBVE8gTyBBQ1VFUkRPLgoKQ09OSUNZVCBpZGVudGlmaWNhcsOhIGNsYXJhbWVudGUgc3Ugbm9tYnJlKGVzKSBjb21vIGVsIGF1dG9yKGVzKSBvIHByb3BpZXRhcmlvKHMpIGRlIGxhIHByZXNlbnRhY2nDs24gLCB5IG5vIGhhcsOhIG5pbmd1bmEgYWx0ZXJhY2nDs24sIGV4Y2VwdG8gc2Vnw7puIGxvIHBlcm1pdGlkbyBwb3IgbGEgbGljZW5jaWEsIHBhcmEgc3UgcHJlc2VudGFjacOzbi4K
score 15,812455

Similares en LA Referencia