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A highly conserved neuronal microexon in DAAM1 controls actin dynamics, RHOA/ROCK signaling, and memory formation

Author

Listed:
  • Patryk Poliński

    (Barcelona Institute of Science and Technology)

  • Marta Miret Cuesta

    (Barcelona Institute of Science and Technology)

  • Alfonsa Zamora-Moratalla

    (Barcelona Institute of Science and Technology)

  • Federica Mantica

    (Barcelona Institute of Science and Technology)

  • Gerard Cantero-Recasens

    (Barcelona Institute of Science and Technology
    Vall d’Hebron Research Institute (VHIR))

  • Carlotta Viana

    (Barcelona Institute of Science and Technology)

  • Miguel Sabariego-Navarro

    (Barcelona Institute of Science and Technology)

  • Davide Normanno

    (Barcelona Institute of Science and Technology
    CNRS)

  • Luis P. Iñiguez

    (Barcelona Institute of Science and Technology)

  • Cruz Morenilla-Palao

    (Instituto de Neurociencias (CSIC-UMH))

  • Patricia Ordoño

    (Instituto de Neurociencias (CSIC-UMH))

  • Sophie Bonnal

    (Barcelona Institute of Science and Technology)

  • Jonathan D. Ellis

    (University of Toronto)

  • Raúl Gómez-Riera

    (Barcelona Institute of Science and Technology)

  • Hugo Fanlo-Ucar

    (Universitat Pompeu Fabra)

  • Dominic S. Yap

    (Barcelona Institute of Science and Technology)

  • María Martínez De Lagrán

    (Barcelona Institute of Science and Technology)

  • Álvaro Fernández-Blanco

    (Barcelona Institute of Science and Technology)

  • Cristina Rodríguez-Marin

    (Barcelona Institute of Science and Technology)

  • Jon Permanyer

    (Barcelona Institute of Science and Technology)

  • Orsolya Fölsz

    (Barcelona Institute of Science and Technology)

  • Eduardo Dominguez-Sala

    (Barcelona Institute of Science and Technology
    Department of Health Sciences)

  • Cesar Sierra

    (Barcelona Institute of Science and Technology)

  • Diana Legutko

    (BRAINCITY)

  • José Wojnacki

    (Barcelona Institute of Science and Technology)

  • Juan Luis Musoles Lleo

    (Barcelona Institute of Science and Technology)

  • Maria Pia Cosma

    (Barcelona Institute of Science and Technology)

  • Francisco José Muñoz

    (Universitat Pompeu Fabra)

  • Benjamin J. Blencowe

    (University of Toronto)

  • Eloisa Herrera

    (Instituto de Neurociencias (CSIC-UMH))

  • Mara Dierssen

    (Barcelona Institute of Science and Technology
    Universitat Pompeu Fabra
    Biomedical Research Networking Center for Rare Diseases (CIBERER))

  • Manuel Irimia

    (Barcelona Institute of Science and Technology
    Universitat Pompeu Fabra
    ICREA)

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.

Suggested Citation

  • Patryk Poliński & Marta Miret Cuesta & Alfonsa Zamora-Moratalla & Federica Mantica & Gerard Cantero-Recasens & Carlotta Viana & Miguel Sabariego-Navarro & Davide Normanno & Luis P. Iñiguez & Cruz More, 2025. "A highly conserved neuronal microexon in DAAM1 controls actin dynamics, RHOA/ROCK signaling, and memory formation," Nature Communications, Nature, vol. 16(1), pages 1-21, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59430-w
    DOI: 10.1038/s41467-025-59430-w
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    References listed on IDEAS

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    1. Eric T. Wang & Rickard Sandberg & Shujun Luo & Irina Khrebtukova & Lu Zhang & Christine Mayr & Stephen F. Kingsmore & Gary P. Schroth & Christopher B. Burge, 2008. "Alternative isoform regulation in human tissue transcriptomes," Nature, Nature, vol. 456(7221), pages 470-476, November.
    2. Shuai Wang & Chelsea DeLeon & Wenfei Sun & Stephen R. Quake & Bryan L. Roth & Thomas C. Südhof, 2024. "Alternative splicing of latrophilin-3 controls synapse formation," Nature, Nature, vol. 626(7997), pages 128-135, February.
    3. Alberto Parras & Héctor Anta & María Santos-Galindo & Vivek Swarup & Ainara Elorza & José L. Nieto-González & Sara Picó & Ivó H. Hernández & Juan I. Díaz-Hernández & Eulàlia Belloc & Annie Rodolosse &, 2018. "Autism-like phenotype and risk gene mRNA deadenylation by CPEB4 mis-splicing," Nature, Nature, vol. 560(7719), pages 441-446, August.
    4. Takanori Otomo & Diana R. Tomchick & Chinatsu Otomo & Sanjay C. Panchal & Mischa Machius & Michael K. Rosen, 2005. "Structural basis of actin filament nucleation and processive capping by a formin homology 2 domain," Nature, Nature, vol. 433(7025), pages 488-494, February.
    5. Jae-Seong Yang & Mireia Garriga-Canut & Nele Link & Carlo Carolis & Katrina Broadbent & Violeta Beltran-Sastre & Luis Serrano & Sebastian P. Maurer, 2018. "rec-YnH enables simultaneous many-by-many detection of direct protein–protein and protein–RNA interactions," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
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