https://hdl.handle.net/20.500.12367/3230 2026-06-01T22:39:11Z 2026-06-01T22:39:11Z Poliński, Patryk Miret Cuesta, Marta Zamora Moratalla, Alfonsa Mantica, Federica Cantero-Recasens, Gerard Viana, Carlotta Sabariego Navarro, Miguel Normanno, Davide Iniguez, Luis P. Morenilla-Palao, Cruz Ordoño Carramiñana, Patricia BONNAL, Sophie Ellis, Jonathan D. Gomez Riera, Raul Fanlo-Ucar, Hugo Yap, Dominic S. martinez de lagran, maria Fernández-Blanco, Álvaro Rodriguez-Marin, Cristina Permanyer, Jon Fölsz, Orsolya Domínguez-Sala, Eduardo Sierra, Cesar Legutko, Diana Wojnacki Fonseca, José Ignacio Musoles Lleo, Juan Luis Cosma, Maria Pia Muñoz, Francisco José Blencowe, Benjamin Herrera, Eloisa Dierssen, Mara Irimia, Manuel https://hdl.handle.net/20.500.12367/3231 2026-06-01T11:21:31Z 2025-05-06T00:00:00Z

A highly conserved neuronal microexon in DAAM1 controls actin dynamics, RHOA/ROCK signaling, and memory formation Poliński, Patryk; Miret Cuesta, Marta; Zamora Moratalla, Alfonsa; Mantica, Federica; Cantero-Recasens, Gerard; Viana, Carlotta; Sabariego Navarro, Miguel; Normanno, Davide; Iniguez, Luis P.; Morenilla-Palao, Cruz; Ordoño Carramiñana, Patricia; BONNAL, Sophie; Ellis, Jonathan D.; Gomez Riera, Raul; Fanlo-Ucar, Hugo; Yap, Dominic S.; martinez de lagran, maria; Fernández-Blanco, Álvaro; Rodriguez-Marin, Cristina; Permanyer, Jon; Fölsz, Orsolya; Domínguez-Sala, Eduardo; Sierra, Cesar; Legutko, Diana; Wojnacki Fonseca, José Ignacio; Musoles Lleo, Juan Luis; Cosma, Maria Pia; Muñoz, Francisco José; Blencowe, Benjamin; Herrera, Eloisa; Dierssen, Mara; Irimia, Manuel 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.

2025-05-06T00:00:00Z