Constitutive and Variable Regions of Z-disk Titin/Connectin in Myofibril Formation: A Dominant-negative Screen

Cell Structure and Function

Paul Young²  Mathias Gautel²  Michelle Peckham¹ 

[1] The Randall Institute, King's College London;European Molecular Biology Laboratory, Structural Biology Division

关键词: titin/connectin;    Z-disk;    sarcomere assembly;    isoforms;   

DOI  :  10.1247/csf.22.95

学科分类：分子生物学，细胞生物学和基因

来源: Japan Society for Cell Biology

【 摘 要 】

References(40)Cited-By(20)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.

【 授权许可】

Unknown