Distinct roles for telethonin N-versus C-terminus in sarcomere assembly and maintenance
Article first published online: 16 MAR 2010
Copyright © 2010 Wiley-Liss, Inc.
Volume 239, Issue 4, pages 1124–1135, April 2010
How to Cite
Sadikot, T., Hammond, C. R. and Ferrari, M. B. (2010), Distinct roles for telethonin N-versus C-terminus in sarcomere assembly and maintenance. Dev. Dyn., 239: 1124–1135. doi: 10.1002/dvdy.22263
- Issue published online: 16 MAR 2010
- Article first published online: 16 MAR 2010
- Manuscript Accepted: 28 JAN 2010
The N-terminus of telethonin forms a unique structure linking two titin N-termini at the Z-disc. While a specific role for the C-terminus has not been established, several studies indicate it may have a regulatory function. Using a morpholino approach in Xenopus, we show that telethonin knockdown leads to embryonic paralysis, myocyte defects, and sarcomeric disruption. These myopathic defects can be rescued by expressing full-length telethonin mRNA in morpholino background, indicating that telethonin is required for myofibrillogenesis. However, a construct missing C-terminal residues is incapable of rescuing motility or sarcomere assembly in cultured myocytes. We, therefore, tested two additional constructs: one where four C-terminal phosphorylatable residues were mutated to alanines and another where terminal residues were randomly replaced. Data from these experiments support that the telethonin C-terminus is required for assembly, but in a context-dependent manner, indicating that factors and forces present in vivo can compensate for C-terminal truncation or mutation. Developmental Dynamics 239:1124–1135, 2010. © 2010 Wiley-Liss, Inc.