title: Constitutive and variable regions of Z-disk titin/connectin in myofibril formation: a dominant-negative screen.
abstract: The giant muscle protein titin (connectin) is assumed to play a crucial role in the control of Z-disk assembly. Analysis of the Z-disk region of titin/connectin revealed a novel 45 residue repeat that is spliced in variable copy numbers. The repeat region is coexpressed in normal human myocardium in size variants corresponding to between 5 and 7 repeats. Smaller isoforms can be detected in muscles with thinner Z-disks like M. psoas. Sequence analysis of chicken breast muscle titin/connectin reveals that in this tissue, where Z-disks are thin, only two Z-repeats are expressed. The greatly variable thickness of Z-disks is therefore correlated to a region of variable length in titin/connectin, constructed from a novel protein building block. Transfection experiments in myogenic cell lines demonstrate that overexpression of the entire integral Z-disk region of titin leads to a disruption of sarcomere assembly. The differentially expressed titin/connectin regions, however, show no dominant-negative effects on myofibril assembly and are not targeted to Z-disks. This supports the idea that the Z-repeat region of titin/connectin is responsible for the control Z-disk thickness as an element of highly variable length, due to extensive differential splicing.
authors.affiliation: European Molecular Biology Laboratory, Structural Biology Division, Heidelberg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Peckham
authors.forename: P
authors.initials: P
authors.lastname: Young
authors.forename: M
authors.initials: M
authors.lastname: Gautel
mesh_terms: D000199:Actins / Q000737:chemistry / Q000502:physiology; D000595:Amino Acid Sequence; D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D002645:Chickens; D064211:Connectin; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000737:chemistry* / Q000235:genetics; D018482:Muscle, Skeletal / Q000166:cytology / Q000648:ultrastructure*; D009210:Myofibrils / Q000737:chemistry* / Q000648:ultrastructure; D011494:Protein Kinases / Q000737:chemistry* / Q000235:genetics; D014162:Transfection
chemical_list: D000199:Actins; D064211:Connectin; D008565:Membrane Proteins; D009124:Muscle Proteins; C577285:TTN protein, human; D011494:Protein Kinases