A functional knock-out of titin results in defective myofibril assembly

van der Ven PFM, Bartsch JW, Gautel M, Jockusch H, Furst DO (2000)
JOURNAL OF CELL SCIENCE 113(8): 1405-1414.

Zeitschriftenaufsatz | Veröffentlicht | Englisch
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van der Ven, PFM; Bartsch, JW; Gautel, M; Jockusch, HaraldUniBi; Furst, DO
Abstract / Bemerkung
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 that only 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. Most importantly, in BHK-21-Bi cells the formation of thick myosin filaments and the assembly of myofibrils are impaired, although sarcomeric proteins are expressed. 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.
BHK-21C/13 cell; null mutation; myofibrillogenesis; myosin assembly; myofibroblast; titin/connectin
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van der Ven PFM, Bartsch JW, Gautel M, Jockusch H, Furst DO. A functional knock-out of titin results in defective myofibril assembly. JOURNAL OF CELL SCIENCE. 2000;113(8):1405-1414.
van der Ven, P. F. M., Bartsch, J. W., Gautel, M., Jockusch, H., & Furst, D. O. (2000). A functional knock-out of titin results in defective myofibril assembly. JOURNAL OF CELL SCIENCE, 113(8), 1405-1414.
van der Ven, P. F. M., Bartsch, J. W., Gautel, M., Jockusch, H., and Furst, D. O. (2000). A functional knock-out of titin results in defective myofibril assembly. JOURNAL OF CELL SCIENCE 113, 1405-1414.
van der Ven, P.F.M., et al., 2000. A functional knock-out of titin results in defective myofibril assembly. JOURNAL OF CELL SCIENCE, 113(8), p 1405-1414.
P.F.M. van der Ven, et al., “A functional knock-out of titin results in defective myofibril assembly”, JOURNAL OF CELL SCIENCE, vol. 113, 2000, pp. 1405-1414.
van der Ven, P.F.M., Bartsch, J.W., Gautel, M., Jockusch, H., Furst, D.O.: A functional knock-out of titin results in defective myofibril assembly. JOURNAL OF CELL SCIENCE. 113, 1405-1414 (2000).
van der Ven, PFM, Bartsch, JW, Gautel, M, Jockusch, Harald, and Furst, DO. “A functional knock-out of titin results in defective myofibril assembly”. JOURNAL OF CELL SCIENCE 113.8 (2000): 1405-1414.

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Chopra A, Kutys ML, Zhang K, Polacheck WJ, Sheng CC, Luu RJ, Eyckmans J, Hinson JT, Seidman JG, Seidman CE, Chen CS., Dev Cell 44(1), 2018
PMID: 29316444
Thick Filament Protein Network, Functions, and Disease Association.
Wang L, Geist J, Grogan A, Hu LR, Kontrogianni-Konstantopoulos A., Compr Physiol 8(2), 2018
PMID: 29687901
Ordering of myosin II filaments driven by mechanical forces: experiments and theory.
Dasbiswas K, Hu S, Schnorrer F, Safran SA, Bershadsky AD., Philos Trans R Soc Lond B Biol Sci 373(1747), 2018
PMID: 29632266
Cardiac cytoarchitecture - why the "hardware" is important for heart function!
Ehler E., Biochim Biophys Acta 1863(7 pt b), 2016
PMID: 26577135
An internal promoter underlies the difference in disease severity between N- and C-terminal truncation mutations of Titin in zebrafish.
Zou J, Tran D, Baalbaki M, Tang LF, Poon A, Pelonero A, Titus EW, Yuan C, Shi C, Patchava S, Halper E, Garg J, Movsesyan I, Yin C, Wu R, Wilsbacher LD, Liu J, Hager RL, Coughlin SR, Jinek M, Pullinger CR, Kane JP, Hart DO, Kwok PY, Deo RC., Elife 4(), 2015
PMID: 26473617
Recessive truncating titin gene, TTN, mutations presenting as centronuclear myopathy.
Ceyhan-Birsoy O, Agrawal PB, Hidalgo C, Schmitz-Abe K, DeChene ET, Swanson LC, Soemedi R, Vasli N, Iannaccone ST, Shieh PB, Shur N, Dennison JM, Lawlor MW, Laporte J, Markianos K, Fairbrother WG, Granzier H, Beggs AH., Neurology 81(14), 2013
PMID: 23975875
Truncations of titin causing dilated cardiomyopathy.
Herman DS, Lam L, Taylor MR, Wang L, Teekakirikul P, Christodoulou D, Conner L, DePalma SR, McDonough B, Sparks E, Teodorescu DL, Cirino AL, Banner NR, Pennell DJ, Graw S, Merlo M, Di Lenarda A, Sinagra G, Bos JM, Ackerman MJ, Mitchell RN, Murry CE, Lakdawala NK, Ho CY, Barton PJ, Cook SA, Mestroni L, Seidman JG, Seidman CE., N Engl J Med 366(7), 2012
PMID: 22335739
Physiologic basis and pathophysiologic implications of the diastolic properties of the cardiac muscle.
Ferreira-Martins J, Leite-Moreira AF., J Biomed Biotechnol 2010(), 2010
PMID: 20625419
Assembly and dynamics of myofibrils.
Sanger JW, Wang J, Fan Y, White J, Sanger JM., J Biomed Biotechnol 2010(), 2010
PMID: 20625425
TC10 controls human myofibril organization and is activated by the sarcomeric RhoGEF obscurin.
Coisy-Quivy M, Touzet O, Bourret A, Hipskind RA, Mercier J, Fort P, Philips A., J Cell Sci 122(pt 7), 2009
PMID: 19258391
Cytoplasmic Ig-domain proteins: cytoskeletal regulators with a role in human disease.
Otey CA, Dixon R, Stack C, Goicoechea SM., Cell Motil Cytoskeleton 66(8), 2009
PMID: 19466753
Disuse-induced preferential loss of the giant protein titin depresses muscle performance via abnormal sarcomeric organization.
Udaka J, Ohmori S, Terui T, Ohtsuki I, Ishiwata S, Kurihara S, Fukuda N., J Gen Physiol 131(1), 2008
PMID: 18166625
Physiological functions of the giant elastic protein titin in mammalian striated muscle.
Fukuda N, Granzier HL, Ishiwata S, Kurihara S., J Physiol Sci 58(3), 2008
PMID: 18477421
Early mechanical dysfunction of the diaphragm in the muscular dystrophy with myositis (Ttnmdm) model.
Lopez MA, Pardo PS, Cox GA, Boriek AM., Am J Physiol Cell Physiol 295(5), 2008
PMID: 18753318
Depletion of zebrafish titin reduces cardiac contractility by disrupting the assembly of Z-discs and A-bands.
Seeley M, Huang W, Chen Z, Wolff WO, Lin X, Xu X., Circ Res 100(2), 2007
PMID: 17170364
The zebrafish runzel muscular dystrophy is linked to the titin gene.
Steffen LS, Guyon JR, Vogel ED, Howell MH, Zhou Y, Weber GJ, Zon LI, Kunkel LM., Dev Biol 309(2), 2007
PMID: 17678642
Muscle atrophy in titin M-line deficient mice.
Peng J, Raddatz K, Labeit S, Granzier H, Gotthardt M., J Muscle Res Cell Motil 26(6-8), 2005
PMID: 16470336
Nebulin regulates the assembly and lengths of the thin filaments in striated muscle.
McElhinny AS, Schwach C, Valichnac M, Mount-Patrick S, Gregorio CC., J Cell Biol 170(6), 2005
PMID: 16157704
M-band: a safeguard for sarcomere stability?
Agarkova I, Ehler E, Lange S, Schoenauer R, Perriard JC., J Muscle Res Cell Motil 24(2-3), 2003
PMID: 14609030


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