Caenorhabditis elegans β-G spectrin is dispensable for establishment of epithelial polarity, but essential for muscular and neuronal function
Caenorhabditis elegans β-G spectrin is dispensable for establishment of epithelial polarity, but essential for muscular and neuronal function
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DOI：
10.1083/jcb.149.4.915
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发表时间：
2000-05-15
影响因子：
7.8
通讯作者：
Bennett, V
中科院分区：
文献类型：
--
作者：
Moorthy, S;Chen, LS;Bennett, V
秀丽隐杆线虫基因组编码一个α血影蛋白亚基、一个β血影蛋白亚基（β-G）和一个β-H血影蛋白亚基。我们的实验表明，C.秀丽线虫α血影蛋白是通过串联消耗β-G和β-H血影蛋白而复制的。我们认为α血影蛋白与β-G和β-H亚基结合形成α/β-G和α/β-H异聚体，这些异聚体在线虫中执行血影蛋白的全部功能。线虫β-G血影蛋白和脊椎动物β-血影蛋白的表达模式表现出三个惊人的相似之处，包括：（1）β-血影蛋白与上皮组织中细胞-细胞接触的位点相关;（2）最高水平的β-G血影蛋白出现在神经系统中;以及（3）横纹肌中的β-血影蛋白-G与肌丝装置与相邻细胞的附着点相关。线虫beta-G血影蛋白与细胞间接触部位的质膜结合，从两细胞阶段开始，在原肠胚形成后，当大多数细胞增殖完成时，其强度急剧增加。引人注目的是，通过RNA介导的干扰将线虫β-G血影蛋白消耗到不可检测的水平并不影响表皮和肠中结构和功能极性的建立。与最近的推测相反，β-G血影蛋白与内膜无关，β-G血影蛋白的耗竭与分泌中任何可检测到的缺陷无关。相反，β-G血影蛋白缺乏的线虫在肌肉组织和神经系统进行性缺陷的早期幼虫时被捕。因此，秀丽隐杆线虫β-G血影蛋白是正常肌肉和神经元功能所必需的，但对于胚胎伸长和早期上皮极性的建立是必需的。我们假设，异聚血影蛋白在后生动物中进化，以响应细胞在机械整合组织的背景下，可以承受由一个活跃的生物体施加的严酷的需要。
The Caenorhabditis elegans genome encodes one alpha spectrin subunit, a beta spectrin subunit (beta-G), and a beta-H spectrin subunit. Our experiments show that the phenotype resulting from the loss of the C. elegans alpha spectrin is reproduced by tandem depletion of both beta-G and beta-H spectrins. We propose that alpha spectrin combines with the beta-G and beta-H subunits to form alpha/beta-G and alpha/beta-H heteromers that perform the entire repertoire of spectrin function in the nematode. The expression patterns of nematode beta-G spectrin and vertebrate beta spectrins exhibit three striking parallels including: (1) beta spectrins are associated with the sites of cell-cell contact in epithelial tissues; (2) the highest levels of beta-G spectrin occur in the nervous system; and (3) beta spectrin-G in striated muscle is associated with points of attachment of the myofilament apparatus to adjacent cells. Nematode beta-G spectrin associates with plasma membranes at sites of cell-cell contact, beginning at the two-cell stage, and with a dramatic increase in intensity after gastrulation when most cell proliferation has been completed. Strikingly, depletion of nematode beta-G spectrin by RNA-mediated interference to undetectable levels does not affect the establishment of structural and functional polarity in epidermis and intestine. Contrary to recent speculation, beta-G spectrin is not associated with internal membranes and depletion of beta-G spectrin was not associated with any detectable defects in secretion. Instead beta-G spectrin-deficient nematodes arrest as early larvae with progressive defects in the musculature and nervous system. Therefore, C,elegans beta-G spectrin is required for normal muscle and neuron function, but is dispensable for embryonic elongation and establishment of early epithelial polarity. We hypothesize that heteromeric spectrin evolved in metazoans in response to the needs of cells in the context of mechanically integrated tissues that can withstand the rigors imposed by an active organism.