Nature Communications (May 2025)
A highly conserved neuronal microexon in DAAM1 controls actin dynamics, RHOA/ROCK signaling, and memory formation
- Patryk Poliński,
- Marta Miret Cuesta,
- Alfonsa Zamora-Moratalla,
- Federica Mantica,
- Gerard Cantero-Recasens,
- Carlotta Viana,
- Miguel Sabariego-Navarro,
- Davide Normanno,
- Luis P. Iñiguez,
- Cruz Morenilla-Palao,
- Patricia Ordoño,
- Sophie Bonnal,
- Jonathan D. Ellis,
- Raúl Gómez-Riera,
- Hugo Fanlo-Ucar,
- Dominic S. Yap,
- María Martínez De Lagrán,
- Álvaro Fernández-Blanco,
- Cristina Rodríguez-Marin,
- Jon Permanyer,
- Orsolya Fölsz,
- Eduardo Dominguez-Sala,
- Cesar Sierra,
- Diana Legutko,
- José Wojnacki,
- Juan Luis Musoles Lleo,
- Maria Pia Cosma,
- Francisco José Muñoz,
- Benjamin J. Blencowe,
- Eloisa Herrera,
- Mara Dierssen,
- Manuel Irimia
Affiliations
- Patryk Poliński
- Centre for Genomic Regulation, Barcelona Institute of Science and Technology
- Marta Miret Cuesta
- Centre for Genomic Regulation, Barcelona Institute of Science and Technology
- Alfonsa Zamora-Moratalla
- Centre for Genomic Regulation, Barcelona Institute of Science and Technology
- Federica Mantica
- Centre for Genomic Regulation, Barcelona Institute of Science and Technology
- Gerard Cantero-Recasens
- Centre for Genomic Regulation, Barcelona Institute of Science and Technology
- Carlotta Viana
- Centre for Genomic Regulation, Barcelona Institute of Science and Technology
- Miguel Sabariego-Navarro
- Centre for Genomic Regulation, Barcelona Institute of Science and Technology
- Davide Normanno
- Centre for Genomic Regulation, Barcelona Institute of Science and Technology
- Luis P. Iñiguez
- Centre for Genomic Regulation, Barcelona Institute of Science and Technology
- Cruz Morenilla-Palao
- Instituto de Neurociencias (CSIC-UMH)
- Patricia Ordoño
- Instituto de Neurociencias (CSIC-UMH)
- Sophie Bonnal
- Centre for Genomic Regulation, Barcelona Institute of Science and Technology
- Jonathan D. Ellis
- Donnelly Centre, University of Toronto
- Raúl Gómez-Riera
- Centre for Genomic Regulation, Barcelona Institute of Science and Technology
- Hugo Fanlo-Ucar
- Universitat Pompeu Fabra
- Dominic S. Yap
- Centre for Genomic Regulation, Barcelona Institute of Science and Technology
- María Martínez De Lagrán
- Centre for Genomic Regulation, Barcelona Institute of Science and Technology
- Álvaro Fernández-Blanco
- Centre for Genomic Regulation, Barcelona Institute of Science and Technology
- Cristina Rodríguez-Marin
- Centre for Genomic Regulation, Barcelona Institute of Science and Technology
- Jon Permanyer
- Centre for Genomic Regulation, Barcelona Institute of Science and Technology
- Orsolya Fölsz
- Centre for Genomic Regulation, Barcelona Institute of Science and Technology
- Eduardo Dominguez-Sala
- Centre for Genomic Regulation, Barcelona Institute of Science and Technology
- Cesar Sierra
- Centre for Genomic Regulation, Barcelona Institute of Science and Technology
- Diana Legutko
- Nencki Institute of Experimental Biology, BRAINCITY
- José Wojnacki
- Centre for Genomic Regulation, Barcelona Institute of Science and Technology
- Juan Luis Musoles Lleo
- Centre for Genomic Regulation, Barcelona Institute of Science and Technology
- Maria Pia Cosma
- Centre for Genomic Regulation, Barcelona Institute of Science and Technology
- Francisco José Muñoz
- Universitat Pompeu Fabra
- Benjamin J. Blencowe
- Donnelly Centre, University of Toronto
- Eloisa Herrera
- Instituto de Neurociencias (CSIC-UMH)
- Mara Dierssen
- Centre for Genomic Regulation, Barcelona Institute of Science and Technology
- Manuel Irimia
- Centre for Genomic Regulation, Barcelona Institute of Science and Technology
- DOI
- https://doi.org/10.1038/s41467-025-59430-w
- Journal volume & issue
-
Vol. 16,
no. 1
pp. 1 – 21
Abstract
Abstract 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.
