A highly conserved neuronal microexon in DAAM1 controls actin dynamics, RHOA/ROCK signaling, and memory formation
Actin cytoskeleton dynamics is essential for proper nervous system development and function. A conserved set of neuronal-specific microexons influences multiple aspects of neurobiology; however, their roles in regulating the actin cytoskeleton are unknown. Here, we study a microexon in DAAM1, a form...
| Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2025 |
| País: | España |
| Institución: | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| Repositorio: | Recercat. Dipósit de la Recerca de Catalunya |
| OAI Identifier: | oai:recercat.cat:10230/70629 |
| Acceso en línea: | http://hdl.handle.net/10230/70629 http://dx.doi.org/10.1038/s41467-025-59430-w |
| Access Level: | acceso abierto |
| Palabra clave: | Biochemistry Learning and memory Molecular biology Molecular neuroscience RNA splicing |
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A highly conserved neuronal microexon in DAAM1 controls actin dynamics, RHOA/ROCK signaling, and memory formation |
| title |
A highly conserved neuronal microexon in DAAM1 controls actin dynamics, RHOA/ROCK signaling, and memory formation |
| spellingShingle |
A highly conserved neuronal microexon in DAAM1 controls actin dynamics, RHOA/ROCK signaling, and memory formation Poliński, Patryk Biochemistry Learning and memory Molecular biology Molecular neuroscience RNA splicing |
| title_short |
A highly conserved neuronal microexon in DAAM1 controls actin dynamics, RHOA/ROCK signaling, and memory formation |
| title_full |
A highly conserved neuronal microexon in DAAM1 controls actin dynamics, RHOA/ROCK signaling, and memory formation |
| title_fullStr |
A highly conserved neuronal microexon in DAAM1 controls actin dynamics, RHOA/ROCK signaling, and memory formation |
| title_full_unstemmed |
A highly conserved neuronal microexon in DAAM1 controls actin dynamics, RHOA/ROCK signaling, and memory formation |
| title_sort |
A highly conserved neuronal microexon in DAAM1 controls actin dynamics, RHOA/ROCK signaling, and memory formation |
| dc.creator.none.fl_str_mv |
Poliński, Patryk Miret-Cuesta, Marta Zamora Moratalla, Alfonsa Mantica, Federica Cantero Recasens, Gerard, 1984- Viana, Carlotta Sabariego Navarro, Miguel Normanno, Davide Iñiguez, Luis P. Bonnal, Sophie Gómez-Riera, Raúl Fanlo-Ucar, Hugo Yap, Dominic S. Martínez de Lagrán Cabredo, María Fernández-Blanco, Álvaro Rodríguez-Marin, Cristina Permanyer, Jon Fölsz, Orsolya Domínguez-Sala, Eduardo Sierra, Cesar Wojnacki, José Musoles Lleo, Juan Luis Cosma, Maria Pia Muñoz López, Francisco José, 1964- Dierssen, Mara Irimia Martínez, Manuel |
| author |
Poliński, Patryk |
| author_facet |
Poliński, Patryk Miret-Cuesta, Marta Zamora Moratalla, Alfonsa Mantica, Federica Cantero Recasens, Gerard, 1984- Viana, Carlotta Sabariego Navarro, Miguel Normanno, Davide Iñiguez, Luis P. Bonnal, Sophie Gómez-Riera, Raúl Fanlo-Ucar, Hugo Yap, Dominic S. Martínez de Lagrán Cabredo, María Fernández-Blanco, Álvaro Rodríguez-Marin, Cristina Permanyer, Jon Fölsz, Orsolya Domínguez-Sala, Eduardo Sierra, Cesar Wojnacki, José Musoles Lleo, Juan Luis Cosma, Maria Pia Muñoz López, Francisco José, 1964- Dierssen, Mara Irimia Martínez, Manuel |
| author_role |
author |
| author2 |
Miret-Cuesta, Marta Zamora Moratalla, Alfonsa Mantica, Federica Cantero Recasens, Gerard, 1984- Viana, Carlotta Sabariego Navarro, Miguel Normanno, Davide Iñiguez, Luis P. Bonnal, Sophie Gómez-Riera, Raúl Fanlo-Ucar, Hugo Yap, Dominic S. Martínez de Lagrán Cabredo, María Fernández-Blanco, Álvaro Rodríguez-Marin, Cristina Permanyer, Jon Fölsz, Orsolya Domínguez-Sala, Eduardo Sierra, Cesar Wojnacki, José Musoles Lleo, Juan Luis Cosma, Maria Pia Muñoz López, Francisco José, 1964- Dierssen, Mara Irimia Martínez, Manuel |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
Biochemistry Learning and memory Molecular biology Molecular neuroscience RNA splicing |
| topic |
Biochemistry Learning and memory Molecular biology Molecular neuroscience RNA splicing |
| description |
Actin cytoskeleton dynamics is essential for proper nervous system development and function. A conserved set of neuronal-specific microexons influences multiple aspects of neurobiology; however, their roles in regulating the actin cytoskeleton are unknown. Here, we study a microexon in DAAM1, a formin-homology-2 (FH2) domain protein involved in actin reorganization. Microexon inclusion extends the linker region of the DAAM1 FH2 domain, altering actin polymerization. Genomic deletion of the microexon leads to neuritogenesis defects and increased calcium influx in differentiated neurons. Mice with this deletion exhibit postsynaptic defects, fewer immature dendritic spines, impaired long-term potentiation, and deficits in memory formation. These phenotypes are associated with increased RHOA/ROCK signaling, which regulates actin-cytoskeleton dynamics, and are partially rescued by treatment with a ROCK inhibitor. This study highlights the role of a conserved neuronal microexon in regulating actin dynamics and cognitive functioning. |
| publishDate |
2025 |
| dc.date.none.fl_str_mv |
2025 2025 2025 |
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info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
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article |
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publishedVersion |
| dc.identifier.none.fl_str_mv |
http://hdl.handle.net/10230/70629 http://dx.doi.org/10.1038/s41467-025-59430-w http://hdl.handle.net/10230/70629 |
| url |
http://hdl.handle.net/10230/70629 http://dx.doi.org/10.1038/s41467-025-59430-w |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.relation.none.fl_str_mv |
Nat Commun. 2025 May 6;16(1):4210 info:eu-repo/grantAgreement/EC/H2020/101002275 info:eu-repo/grantAgreement/ES/2PE/PID2020-115040GB-I00 info:eu-repo/grantAgreement/ES/3PE/PID2022−141900OB-I00 info:eu-repo/grantAgreement/ES/2PE/PID2020-114080GB-I00 info:eu-repo/grantAgreement/ES/3PE/PID2023-1497670B-I00 info:eu-repo/grantAgreement/ES/3PE/PID2022-138245NB-I00 info:eu-repo/grantAgreement/EC/H2020/964342 info:eu-repo/grantAgreement/EC/H2020/721890 info:eu-repo/grantAgreement/EC/H2020/848077 |
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http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess |
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http://creativecommons.org/licenses/by-nc-nd/4.0/ |
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openAccess |
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application/pdf application/pdf |
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Nature Research |
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Nature Research |
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reponame:Recercat. Dipósit de la Recerca de Catalunya instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
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Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
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Recercat. Dipósit de la Recerca de Catalunya |
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Recercat. Dipósit de la Recerca de Catalunya |
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1869420631197483008 |
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A highly conserved neuronal microexon in DAAM1 controls actin dynamics, RHOA/ROCK signaling, and memory formationPoliński, PatrykMiret-Cuesta, MartaZamora Moratalla, AlfonsaMantica, FedericaCantero Recasens, Gerard, 1984-Viana, CarlottaSabariego Navarro, MiguelNormanno, DavideIñiguez, Luis P.Bonnal, SophieGómez-Riera, RaúlFanlo-Ucar, HugoYap, Dominic S.Martínez de Lagrán Cabredo, MaríaFernández-Blanco, ÁlvaroRodríguez-Marin, CristinaPermanyer, JonFölsz, OrsolyaDomínguez-Sala, EduardoSierra, CesarWojnacki, JoséMusoles Lleo, Juan LuisCosma, Maria PiaMuñoz López, Francisco José, 1964-Dierssen, MaraIrimia Martínez, ManuelBiochemistryLearning and memoryMolecular biologyMolecular neuroscienceRNA splicingActin cytoskeleton dynamics is essential for proper nervous system development and function. A conserved set of neuronal-specific microexons influences multiple aspects of neurobiology; however, their roles in regulating the actin cytoskeleton are unknown. Here, we study a microexon in DAAM1, a formin-homology-2 (FH2) domain protein involved in actin reorganization. Microexon inclusion extends the linker region of the DAAM1 FH2 domain, altering actin polymerization. Genomic deletion of the microexon leads to neuritogenesis defects and increased calcium influx in differentiated neurons. Mice with this deletion exhibit postsynaptic defects, fewer immature dendritic spines, impaired long-term potentiation, and deficits in memory formation. These phenotypes are associated with increased RHOA/ROCK signaling, which regulates actin-cytoskeleton dynamics, and are partially rescued by treatment with a ROCK inhibitor. This study highlights the role of a conserved neuronal microexon in regulating actin dynamics and cognitive functioning.The research has been funded by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (ERCCoG-LS2-101002275 to M.I.), Spanish Ministry of Science and Innovation (PID2020-115040GB-I00 to M.I., PID2022−141900OB-I00 to M.D., PID2020- 114080GB-I00 to M.P.C., PID2023-1497670B-I00 to F.J.M. and PID2022-138245NB-I00 to E.H), the European Union’s Horizon 2020 research and innovation program under grant agreements No 964342 to M.P.C., 721890 to P.P. and 848077 to A.Z.M., the National Institutes of Health (NIH) (1R01NS137222-01 to M.D.) and AGAUR grants from Secretaria d’Universitats i Recerca del Departament d’Empresa iConeixement de la Generalitat de Catalunya to M.I., M.D. and M.P.C.. CRG acknowledges support of the Spanish Ministry of Science and Innovation through the Centro de Excelencia Severo Ochoa (CEX2020-001049-S, MCIN/AEI/10.13039/501100011033), and the Generalitat de Catalunya through the CERCA program. M.S.N. received an FPU fellowship (FPU19/04789) from Ministerio de Universidades. This research was in part supported by grants from the Simons Foundation and Canadian Institutes of Health Research to B.J.B., who also holds the University of Toronto Banbury Chair in Medical Research and the Canada Research Chair in RNA Biology and Genomics.Nature Research202520252025info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/70629http://dx.doi.org/10.1038/s41467-025-59430-whttp://hdl.handle.net/10230/70629reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésNat Commun. 2025 May 6;16(1):4210info:eu-repo/grantAgreement/EC/H2020/101002275info:eu-repo/grantAgreement/ES/2PE/PID2020-115040GB-I00info:eu-repo/grantAgreement/ES/3PE/PID2022−141900OB-I00info:eu-repo/grantAgreement/ES/2PE/PID2020-114080GB-I00info:eu-repo/grantAgreement/ES/3PE/PID2023-1497670B-I00info:eu-repo/grantAgreement/ES/3PE/PID2022-138245NB-I00info:eu-repo/grantAgreement/EC/H2020/964342info:eu-repo/grantAgreement/EC/H2020/721890info:eu-repo/grantAgreement/EC/H2020/848077© The Author(s) 2025. 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To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.http://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:10230/706292026-05-29T05:05:01Z |
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