Mutations in the drosophila orthologs of the F-actin capping protein α- and β-subunits cause actin accumulation and subsequent retinal degeneration
Mutations in the drosophila orthologs of the F-actin capping protein α- and β-subunits cause actin accumulation and subsequent retinal degeneration
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DOI：
10.1534/genetics.105.049213
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发表时间：
2005-12-01
期刊：
影响因子：
3.3
通讯作者：
Hariharan, IK
中科院分区：
文献类型：
--
作者：
Delalle, I;Pfleger, CM;Hariharan, IK
几种人类神经退行性疾病的进展的特征在于细胞内包涵体或细胞骨架异常的出现。一个重要的问题是，这些异常是否真的有助于退化过程，或者它们是否仅仅是已经注定要退化的细胞的表现。我们在果蝇中进行了一次大规模的筛选，以寻找在眼睛发育过程中改变细胞生长或分化的突变。我们利用有丝分裂重组产生了一片纯合的突变细胞。在我们的整个筛选中，只有两个不同位点的突变，烧伤（bnd）和烧焦（scorched），导致眼睛中的突变斑块出现黑色，突变组织似乎经历了退化。在幼虫成虫盘，生长和细胞命运规范正常发生在突变细胞，但有一个积累的F-肌动蛋白。突变细胞在蛹发育阶段退化得更晚。烧焦突变与先前描述的编码F-肌动蛋白加帽蛋白的P-亚基的cpb基因座中的突变是等位的，而烧焦突变破坏编码其α-亚基（cpa）的基因。α/β-异源二聚体覆盖肌动蛋白丝的倒刺末端并限制其生长。在缺乏肌动蛋白的情况下，细胞逐渐积累肌动蛋白丝并最终死亡。他们的人类直系同源物在神经退行性疾病中的可能作用值得进一步研究。
The progression of several human neurodegenerative diseases is characterized by the appearance of intracellular inclusions or cytoskeletal abnormalities. An important question is whether these abnormalities actually contribute to the degenerative process or whether they are merely manifestations of cells that are already destined for degeneration. We have conducted a large screen in Drosophila for mutations that alter the growth or differentiation of cells during eye development. We have used mitotic recombination to generate patches of homozygous Mutant cells. In our entire screen, mutations in only two different loci, burned (bnd) and scorched (scrd), resulted in eyes in which the mutant patches appeared black and the mutant tissue appeared to have undergone degeneration. In larval imaginal discs, growth and cell fate specification occur normally in mutant cells, but there is an accumulation of F-actin. Mutant cells degenerate much later during the pupal phase of development. burned mutations are allelic to mutations in the previously described cpb locus that encodes the P-subunit of the F-actin capping protein, while scorched mutations disrupt the gene encoding its a-subunit (cpa). The alpha/beta-heterodimer caps the barbed ends of an actin filament and restricts its growth. In its absence, cells progressively accumulate actin filaments and eventually die. A possible role for their human orthologs in neurodegenerative disease merits further investigation.