The ALP-Enigma Protein ALP-1 Functions in Actin Filament Organization to Promote Muscle Structural Integrity in Caenorhabditis elegans
The ALP-Enigma Protein ALP-1 Functions in Actin Filament Organization to Promote Muscle Structural Integrity in Caenorhabditis elegans
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DOI：
10.1091/mbc.e08-06-0584
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发表时间：
2009-05-01
影响因子：
3.3
通讯作者：
Beckerle, Mary C.
中科院分区：
文献类型：
--
作者：
Han, Hsiao-Fen;Beckerle, Mary C.
影响Z盘相关ALP-Enigma蛋白的突变与人类肌肉和心脏疾病有关。尽管它们对人类健康具有明确的生理意义，但ALP-Enigma蛋白的作用机制在很大程度上是未知的。在秀丽隐杆线虫中，ALP-Enigma蛋白家族由单个基因alp-1编码; elegans为研究ALP-Enigma功能提供了一个很好的模型。在这里，我们提出了一个分子和遗传分析的ALP-Enigma功能在C。优雅的。我们发现，ALP-1和α-辅肌动蛋白共定位在致密的机构，肌动蛋白丝锚定和ALP-1在致密的机构的适当的本地化是依赖于α-辅肌动蛋白。我们对ALP-1突变体的分析表明，ALP-1的功能是维持肌动蛋白丝的组织，并在收缩过程中参与肌肉稳定。降低α-辅肌动蛋白活性增强了ALP-1突变体的肌动蛋白丝表型，表明ALP-1和α-辅肌动蛋白在相同的细胞过程中起作用。与α-辅肌动蛋白一样，alp-1也与连接蛋白/肌联蛋白家族成员ketn-1在遗传上相互作用，为支持体壁肌肉收缩提供机械稳定性。综上所述，我们的数据表明，ALP-1和α-辅肌动蛋白一起发挥作用，以稳定肌动蛋白丝，促进肌肉结构的完整性。
Mutations that affect the Z-disk-associated ALP-Enigma proteins have been linked to human muscular and cardiac diseases. Despite their clear physiological significance for human health, the mechanism of action of ALP-Enigma proteins is largely unknown. In Caenorhabditis elegans, the ALP-Enigma protein family is encoded by a single gene, alp-1; thus C. elegans provides an excellent model to study ALP-Enigma function. Here we present a molecular and genetic analysis of ALP-Enigma function in C. elegans. We show that ALP-1 and alpha-actinin colocalize at dense bodies where actin filaments are anchored and that the proper localization of ALP-1 at dense bodies is dependent on alpha-actinin. Our analysis of alp-1 mutants demonstrates that ALP-1 functions to maintain actin filament organization and participates in muscle stabilization during contraction. Reducing alpha-actinin activity enhances the actin filament phenotype of the alp-1 mutants, suggesting that ALP-1 and alpha-actinin function in the same cellular process. Like alpha-actinin, alp-1 also interacts genetically with a connectin/titin family member, ketn-1, to provide mechanical stability for supporting body wall muscle contraction. Taken together, our data demonstrate that ALP-1 and alpha-actinin function together to stabilize actin filaments and promote muscle structural integrity.