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Distinct roles for telethonin N‐versus C‐terminus in sarcomere assembly and maintenance
Author(s) -
Sadikot Takrima,
Hammond Courtney R.,
Ferrari Michael B.
Publication year - 2010
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.22263
Subject(s) - titin , biology , sarcomere , c terminus , morpholino , microbiology and biotechnology , context (archaeology) , xenopus , gene knockdown , biochemistry , myocyte , gene , amino acid , paleontology
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.