The role of Drosophila Lamin C in muscle function and gene expression
The role of Drosophila Lamin C in muscle function and gene expression
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DOI：
10.1242/dev.048231
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发表时间：
2010-09-15
期刊：
影响因子：
4.6
通讯作者：
Wallrath, Lori L.
中科院分区：
文献类型：
--
作者：
Dialynas, George;Speese, Sean;Wallrath, Lori L.
核膜(NE)的内侧排列着板层，这是一个由中间细丝组成的网络，为核提供结构支持，并在许多核过程中发挥作用。Lamins根据生化特性分为A-型或B-型，具有保守的球状头部、中央杆状结构域和包含Ig-折叠结构基序的C-末端结构域。在人类中，A型板层的突变会导致表现出组织特异性缺陷的疾病，如Emery-Dreifuss肌营养不良症。果蝇正被用作确定A-型层蛋白在发育过程中的组织特异性功能的模型，这对理解人类疾病机制具有重要意义。GAL4-UAS系统用于在野生型背景下表达野生型和突变型的Lamin C(推测为果蝇A型Lamin)。野生型果蝇Lamin C的幼虫肌肉特异性表达没有引起明显的表型。相比之下，缺乏N端头的Lamin C截短形式的幼虫肌肉特异性表达(Lamin C Delta N)会导致肌肉缺陷和半致死性，成年的“逃跑者”拥有畸形的腿。腿的缺陷是由于幼虫缺乏肌肉功能和激素调节基因表达的变化。通过靶向报告基因上游的Lamin C DNA结合域融合蛋白，直接测试了Lamin C与基因关联的后果。Lamin C的结合与报告基因在核周的定位和基因抑制有关。这些数据表明了果蝇A型层粘连蛋白、激素诱导的基因表达和肌肉功能之间的联系。
The inner side of the nuclear envelope (NE) is lined with lamins, a meshwork of intermediate filaments that provides structural support for the nucleus and plays roles in many nuclear processes. Lamins, classified as A- or B-types on the basis of biochemical properties, have a conserved globular head, central rod and C-terminal domain that includes an Ig-fold structural motif. In humans, mutations in A-type lamins give rise to diseases that exhibit tissue-specific defects, such as Emery-Dreifuss muscular dystrophy. Drosophila is being used as a model to determine tissue-specific functions of A-type lamins in development, with implications for understanding human disease mechanisms. The GAL4-UAS system was used to express wild-type and mutant forms of Lamin C (the presumed Drosophila A-type lamin), in an otherwise wild-type background. Larval muscle-specific expression of wild type Drosophila Lamin C caused no overt phenotype. By contrast, larval muscle-specific expression of a truncated form of Lamin C lacking the N-terminal head (Lamin C Delta N) caused muscle defects and semi-lethality, with adult 'escapers' possessing malformed legs. The leg defects were due to a lack of larval muscle function and alterations in hormone-regulated gene expression. The consequences of Lamin C association at a gene were tested directly by targeting a Lamin C DNA-binding domain fusion protein upstream of a reporter gene. Association of Lamin C correlated with localization of the reporter gene at the nuclear periphery and gene repression. These data demonstrate connections among the Drosophila A-type lamin, hormone-induced gene expression and muscle function.