Poliński, 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, Manuel2025-06-052025-06-052025Poliński P, Miret Cuesta M, Zamora-Moratalla A, Mantica F, Cantero-Recasens G, Viana C, et al. A highly conserved neuronal microexon in DAAM1 controls actin dynamics, RHOA/ROCK signaling, and memory formation. Nat Commun. 2025 May 6;16(1):4210. DOI: 10.1038/s41467-025-59430-w2041-1723http://hdl.handle.net/10230/70629Actin 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.application/pdfeng© The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.info:eu-repo/semantics/articlehttp://dx.doi.org/10.1038/s41467-025-59430-wBiochemistryLearning and memoryMolecular biologyMolecular neuroscienceRNA splicinginfo:eu-repo/semantics/openAccess