Drosophila Tropomodulin is required for multiple actin-dependent processes within developing myofibers.

Autor:	Zapater I Morales C; Biochemistry, Cell & Developmental Biology, and Molecular Biology (BCMB) program, Weill Cornell Graduate School of Medical Sciences, New York, NY 10065, USA.; Developmental Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering, Cancer Center, New York, NY 10065, USA., Carman PJ; Biochemistry and Molecular Biophysics Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.; Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA., Soffar DB; Developmental Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering, Cancer Center, New York, NY 10065, USA., Windner SE; Developmental Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering, Cancer Center, New York, NY 10065, USA., Dominguez R; Biochemistry and Molecular Biophysics Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.; Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA., Baylies MK; Biochemistry, Cell & Developmental Biology, and Molecular Biology (BCMB) program, Weill Cornell Graduate School of Medical Sciences, New York, NY 10065, USA.; Developmental Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering, Cancer Center, New York, NY 10065, USA.
Jazyk:	angličtina
Zdroj:	Development (Cambridge, England) [Development] 2023 Mar 15; Vol. 150 (6). Date of Electronic Publication: 2023 Mar 24.
DOI:	10.1242/dev.201194
Abstrakt:	Proper muscle contraction requires the assembly and maintenance of sarcomeres and myofibrils. Although the protein components of myofibrils are generally known, less is known about the mechanisms by which they individually function and together synergize for myofibril assembly and maintenance. For example, it is unclear how the disruption of actin filament (F-actin) regulatory proteins leads to the muscle weakness observed in myopathies. Here, we show that knockdown of Drosophila Tropomodulin (Tmod), results in several myopathy-related phenotypes, including reduction of muscle cell (myofiber) size, increased sarcomere length, disorganization and misorientation of myofibrils, ectopic F-actin accumulation, loss of tension-mediating proteins at the myotendinous junction, and misshaped and internalized nuclei. Our findings support and extend the tension-driven self-organizing myofibrillogenesis model. We show that, like its mammalian counterpart, Drosophila Tmod caps F-actin pointed-ends, and we propose that this activity is crucial for cellular processes in different locations within the myofiber that directly and indirectly contribute to the maintenance of muscle function. Our findings provide significant insights to the role of Tmod in muscle development, maintenance and disease. Competing Interests: Competing interests The authors declare no competing or financial interests. (© 2023. Published by The Company of Biologists Ltd.)
Databáze:	MEDLINE
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