Distinct roles for telethonin N-versus C-terminus in sarcomere assembly and maintenance.
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
Takrima
T
Division of Molecular Biology and Biochemistry, School of Biological Sciences, University of Missouri, Kansas City, Missouri 64110, USA.
Hammond
Courtney R
CR
Ferrari
Michael B
MB
D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D004625:Embryo, Nonmammalian; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D008958:Models, Molecular; D024510:Muscle Development / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D018485:Muscle Fibers, Skeletal / Q000378:metabolism / Q000502:physiology; D009124:Muscle Proteins / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D054792:Muscle, Striated / Q000254:growth & development / Q000378:metabolism / Q000502:physiology; D020320:Oligoribonucleotides, Antisense / Q000494:pharmacology; D017434:Protein Structure, Tertiary / Q000235:genetics / Q000502:physiology; D012518:Sarcomeres / Q000187:drug effects / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D017385:Sequence Homology; D014981:Xenopus
D009124:Muscle Proteins; D020320:Oligoribonucleotides, Antisense