Telethonin knockdown causes embryonic paralysis and sarcomeric disruption, and while the C-terminus is required for assembly in vitro, in vivo factors can compensate for its truncation or mutation.
The telethonin C-terminus is required for sarcomere assembly in a context-dependent manner, with in vivo factors able to compensate for its truncation or mutation.
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.
Sadikot et al. (Tue,) conducted a other in Myocyte defects and sarcomeric disruption. Telethonin knockdown and C-terminal mutation/truncation vs. Full-length telethonin mRNA was evaluated on Sarcomere assembly and motility. Telethonin knockdown causes embryonic paralysis and sarcomeric disruption, and while the C-terminus is required for assembly in vitro, in vivo factors can compensate for its truncation or mutation.
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