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The Crumbs_C isoform of?Drosophila?shows tissue- and stage-specific expression and prevents light-dependent retinal degeneration

机译:果蝇的Crunbs_C亚型显示组织和阶段特异性表达,并防止光依赖性视网膜变性

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Drosophila?Crumbs (Crb) is a key regulator of epithelial polarity and fulfils a plethora of other functions, such as growth regulation, morphogenesis of photoreceptor cells and prevention of retinal degeneration. This raises the question how a single gene regulates such diverse functions, which in mammals are controlled by three different paralogs. Here, we show that in?Drosophila?different Crb protein isoforms are differentially expressed as a result of alternative splicing. All isoforms are transmembrane proteins that differ by just one EGF-like repeat in their extracellular portion. Unlike Crb_A, which is expressed in most embryonic epithelia from early stages onward, Crb_C is expressed later and only in a subset of embryonic epithelia. Flies specifically lacking Crb_C are homozygous viable and fertile. Strikingly, these flies undergo light-dependent photoreceptor degeneration despite the fact that the other isoforms are expressed and properly localised at the stalk membrane. This allele now provides an ideal possibility to further unravel the molecular mechanisms by which?Drosophila crb?protects photoreceptor cells from the detrimental consequences of light-induced cell stress.
机译:果蝇?面包屑(Crb)是上皮极性的关键调节器,并具有许多其他功能,例如生长调节,感光细胞的形态发生和视网膜变性的预防。这就提出了一个问题,即单个基因如何调节这种多样化的功能,而这种功能在哺乳动物中是由三种不同的旁系同源物控制的。在这里,我们显示了在果蝇中不同的Crb蛋白同工型由于选择性剪接而差异表达。所有同工型都是跨膜蛋白,在其细胞外部分仅存在一个类似EGF的重复。与Crb_A从早期开始在大多数胚胎上皮细胞中表达不同,Crb_C在晚期表达,并且仅在一部分胚胎上皮细胞中表达。特别缺乏Crb_C的果蝇是纯合的且能育。令人惊讶的是,尽管其他同工型在茎膜上表达并正确定位,但这些果蝇仍经历了光依赖性光感受器退化。现在,该等位基因为进一步阐明“果蝇crb”保护光感受器细胞免受光诱导的细胞应激的有害影响的分子机制提供了理想的可能性。

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