Critical roles for multiple formins during cardiac myofibril development and repair

Michelle Rosado, Cynthia F. Barber, Cristina Berciu, Steven Feldman, Susan J. Birren, Daniela Nicastro, Bruce L. Goode

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Cardiac and skeletal muscle function depends on the proper formation of myofibrils, which are tandem arrays of highly organized actomyosin contractile units called sarcomeres. How the architecture of these colossal molecular assemblages is established during development and maintained over the lifetime of an animal is poorly understood. We investigate the potential roles in myofibril formation and repair of formin proteins, which are encoded by 15 different genes in mammals. Using quantitative real-time PCR analysis, we find that 13 formins are differentially expressed in mouse hearts during postnatal development. Seven formins immunolocalize to sarcomeres in diverse patterns, suggesting that they have a variety of functional roles. Using RNA interference silencing, we find that the formins mDia2, DAAM1, FMNL1, and FMNL2 are required nonredundantly for myofibrillogenesis. Knockdown phenotypes include global loss of myofibril organization and defective sarcomeric ultrastructure. Finally, our analysis reveals an unanticipated requirement specifically for FMNL1 and FMNL2 in the repair of damaged myofibrils. Together our data reveal an unexpectedly large number of formins, with diverse localization patterns and nonredundant roles, functioning in myofibril development and maintenance, and provide the first evidence of actin assembly factors being required to repair myofibrils.

Original languageEnglish (US)
Pages (from-to)811-827
Number of pages17
JournalMolecular biology of the cell
Volume25
Issue number6
DOIs
StatePublished - Mar 15 2014

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Critical roles for multiple formins during cardiac myofibril development and repair'. Together they form a unique fingerprint.

  • Cite this

    Rosado, M., Barber, C. F., Berciu, C., Feldman, S., Birren, S. J., Nicastro, D., & Goode, B. L. (2014). Critical roles for multiple formins during cardiac myofibril development and repair. Molecular biology of the cell, 25(6), 811-827. https://doi.org/10.1091/mbc.E13-08-0443