期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 109, 期 44, 页码 17983-17988出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1208408109
关键词
muscle degeneration; TRIM protein; LGMD2H
资金
- National Institutes of Health [AR059311, AR060788]
- Muscular Dystrophy Association [176329]
- American Heart Association [080206Z]
- National Institute of General Medical Sciences/Initiative for Maximizing Student Development (IMSD) [5R25GM060201]
Myofibril stability is required for normal muscle function and maintenance. Mutations that disrupt myofibril stability result in individuals who develop progressive muscle wasting, or muscular dystrophy, and premature mortality. Here we present our investigations of the Drosophila l(2)thin [l(2)tn] mutant. The thin phenotype exhibits features of the human muscular disease phenotype in that tn mutant larvae show progressive muscular degeneration. Loss-of-function and rescue experiments determined that l(2) tn is allelic to the tn locus [previously annotated as both CG15105 and another b-box affiliate (abba)]. tn encodes a TRIM (tripartite motif) containing protein highly expressed in skeletal muscle and is orthologous to the human limb-girdle muscular dystrophy type 2H disease gene Trim32. Thin protein is localized at the Z-disk in muscle, but l(2)tn mutants showed no genetic interaction with mutants affecting the Z-line-associated protein muscle LIM protein 84B. l(2)tn, along with loss-of-function mutants generated for tn, showed no relative mislocalization of the Z-disk proteins alpha-Actinin and muscle LIM protein 84B. In contrast, tn mutants had significant disorganization of the costameric orthologs beta-integrin, Spectrin, Talin, and Vinculin, and we present the initial description for the costamere, a key muscle stability complex, in Drosophila. Our studies demonstrate that myofibrils progressively unbundle in flies that lack Thin function through progressive costamere breakdown. Due to the high conservation of these structures in animals, we demonstrate a previously unknown role for TRIM32 proteins in myofibril stability.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据