Tuning Passive Mechanics through Differential Splicing of Titin during Skeletal Muscle Development
AUTOR(ES)
Ottenheijm, Coen A.C.
FONTE
The Biophysical Society
RESUMO
During postnatal development, major changes in mechanical properties of skeletal muscle occur. We investigated passive properties of skeletal muscle in mice and rabbits that varied in age from 1 day to ∼1 year. Neonatal skeletal muscle expressed large titin isoforms directly after birth, followed by a gradual switch toward progressively smaller isoforms that required weeks-to-months to be completed. This suggests an extremely high plasticity of titin splicing during skeletal muscle development. Titin exon microarray analysis showed increased expression of a large group of exons in neonatal muscle, when compared to adult muscle transcripts, with the majority of upregulated exons coding for the elastic proline-glutamate-valine-lysine (PEVK) region of titin. Protein analysis supported expression of a significantly larger PEVK segment in neonatal muscle. In line with these findings, we found >50% lower titin-based passive stiffness of neonatal muscle when compared to adult muscle. Inhibiting 3,5,3′-tri-iodo-L-thyronine and 3,5,3′,5′-tetra-iodo-L-thyronine secretion did not alter isoform switching, suggesting no major role for thyroid hormones in regulating differential titin splicing during postnatal development. In summary, our work shows that stiffening of skeletal muscle during postnatal development occurs through a decrease in titin isoform size, due mainly to a marked restructuring of the PEVK region of titin.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2764098Documentos Relacionados
- Passive stiffness of rat skeletal muscle undernourished during fetal development
- Nature of PEVK-titin elasticity in skeletal muscle
- Association of titin and myosin heavy chain in developing skeletal muscle.
- Evidence for sequential expression of multiple AMP deaminase isoforms during skeletal muscle development.
- Regulation of Myosin Heavy Chain Expression during Rat Skeletal Muscle Development In Vitro