Abstract:
: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 approximately 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.
journal_name
Biophys Jjournal_title
Biophysical journalauthors
Ottenheijm CA,Knottnerus AM,Buck D,Luo X,Greer K,Hoying A,Labeit S,Granzier Hdoi
10.1016/j.bpj.2009.07.041subject
Has Abstractpub_date
2009-10-21 00:00:00pages
2277-86issue
8eissn
0006-3495issn
1542-0086pii
S0006-3495(09)01304-6journal_volume
97pub_type
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