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Titolo:
A functional knock-out of titin results in defective myofibril assembly
Autore:
van der Ven, PFM; Bartsch, JW; Gautel, M; Jockusch, H; Furst, DO;
Indirizzi:
Univ Potsdam, Dept Cell Biol, D-14471 Potsdam, Germany Univ Potsdam Potsdam Germany D-14471 Cell Biol, D-14471 Potsdam, Germany Univ Bielefeld, D-4800 Bielefeld, Germany Univ Bielefeld Bielefeld Germany D-4800 efeld, D-4800 Bielefeld, Germany Max Planck Inst Mol Physiol, D-44139 Dortmund, Germany Max Planck Inst MolPhysiol Dortmund Germany D-44139 9 Dortmund, Germany
Titolo Testata:
JOURNAL OF CELL SCIENCE
fascicolo: 8, volume: 113, anno: 2000,
pagine: 1405 - 1414
SICI:
0021-9533(200004)113:8<1405:AFKOTR>2.0.ZU;2-P
Fonte:
ISI
Lingua:
ENG
Soggetto:
BINDING-PROTEIN-C; SARCOMERIC M-BAND; FAMILIAL HYPERTROPHIC CARDIOMYOPATHY; REGULATORY PHOSPHORYLATION SITE; SKELETAL-MUSCLE CELLS; Z-LINE REGION; MYOSIN-BINDING; STRIATED-MUSCLE; IMMUNOELECTRON MICROSCOPY; THICK FILAMENTS;
Keywords:
titin/connectin; BHK-21C/13 cell; null mutation; myofibrillogenesis; myofibroblast; myosin assembly;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
68
Recensione:
Indirizzi per estratti:
Indirizzo: van der Ven, PFM Univ Potsdam, Dept Cell Biol, Lennestr 7A, D-14471 Potsdam, Germany Univ Potsdam Lennestr 7A Potsdam Germany D-14471 Germany
Citazione:
P.F.M. van der Ven et al., "A functional knock-out of titin results in defective myofibril assembly", J CELL SCI, 113(8), 2000, pp. 1405-1414

Abstract

Titin, also called connectin, is a giant muscle protein that spans the distance from the sarcomeric Z-disc to the M-band. Titin is thought to direct the assembly of sarcomeres and to maintain sarcomeric integrity by interacting with numerous sarcomeric proteins and providing a mechanical linkage. Since severe defects of such an important molecule are likely to result in embryonic lethality, a cell culture model should offer the best practicable tool to probe the cellular functions of titin. The myofibroblast cell line BHK-21/C13 was described to assemble myofibrils in culture. We have now characterized the sub-line BHK-21-Bi, which bears a small deletion within the titin gene. RNA analysis revealed that in this mutant cell line only a small internal portion of the titin mRNA is deleted. However, western blots, immunofluorescence microscopy and immunoprecipitation experiments showed thatonly the N-terminal, approx. 100 kDa central Z-disc portion of the 3 MDa titin protein is expressed, due to the homozygous deletion in the gene. Mostimportantly, in BHK-21-Bi cells the formation of thick myosin filaments and the assembly of myofibrils are impaired, although sarcomeric proteins areexpressed. Lack of thick filament formation and of ordered actin-myosin arrays was confirmed by electron microscopy. Myogenisation induced by transfection with MyoD yielded myofibrils only in myotubes formed from wild type and not from mutant cells, ruling out that a principal failure in myogenic commitment of the BHK-21-Bi cells might cause the observed effects. These experiments provide the first direct evidence for the crucial role of titin in both thick filament formation as a molecular ruler and in the coordination of myofibrillogenesis.

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Documento generato il 03/12/20 alle ore 15:45:45