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Dysfunction of Oskyddad causes Harlequin-type ichthyosis-like defects in Drosophila melanogaster.
PLOS Genetics ( IF 4.5 ) Pub Date : 2020-01-13 , DOI: 10.1371/journal.pgen.1008363
Yiwen Wang 1, 2 , Michaela Norum 1 , Kathrin Oehl 1 , Yang Yang 1 , Renata Zuber 1, 3 , Jing Yang 1 , Jean-Pierre Farine 4 , Nicole Gehring 1 , Matthias Flötenmeyer 5 , Jean-François Ferveur 4 , Bernard Moussian 1, 6
Affiliation  

Prevention of desiccation is a constant challenge for terrestrial organisms. Land insects have an extracellular coat, the cuticle, that plays a major role in protection against exaggerated water loss. Here, we report that the ABC transporter Oskyddad (Osy)-a human ABCA12 paralog-contributes to the waterproof barrier function of the cuticle in the fruit fly Drosophila melanogaster. We show that the reduction or elimination of Osy function provokes rapid desiccation. Osy is also involved in defining the inward barrier against xenobiotics penetration. Consistently, the amounts of cuticular hydrocarbons that are involved in cuticle impermeability decrease markedly when Osy activity is reduced. GFP-tagged Osy localises to membrane nano-protrusions within the cuticle, likely pore canals. This suggests that Osy is mediating the transport of cuticular hydrocarbons (CHC) through the pore canals to the cuticle surface. The envelope, which is the outermost cuticle layer constituting the main barrier, is unaffected in osy mutant larvae. This contrasts with the function of Snu, another ABC transporter needed for the construction of the cuticular inward and outward barriers, that nevertheless is implicated in CHC deposition. Hence, Osy and Snu have overlapping and independent roles to establish cuticular resistance against transpiration and xenobiotic penetration. The osy deficient phenotype parallels the phenotype of Harlequin ichthyosis caused by mutations in the human abca12 gene. Thus, it seems that the cellular and molecular mechanisms of lipid barrier assembly in the skin are conserved during evolution.

中文翻译:

Oskyddad的功能障碍会导致果蝇的Harlequin型鱼鳞病样缺陷。

对于陆地生物而言,防止干燥是一个持续的挑战。陆地昆虫具有细胞外被膜,即角质层,在防止过度失水方面起着重要作用。在这里,我们报告说,ABC转运蛋白Oskyddad(Osy)-人类ABCA12旁系同源物有助于果蝇果蝇的表皮的防水屏障功能。我们表明减少或消除Osy功能会引起快速干燥。Osy还参与定义阻止异种生物渗透的内向障碍。一致地,当Osy活性降低时,涉及表皮不渗透性的表皮碳氢化合物的量显着降低。带有GFP标签的Osy定位于角质层内的膜纳米突起,可能是孔道。这表明Osy正在介导表皮碳氢化合物(CHC)穿过毛细血管到达表皮表面。包膜是构成主要屏障的最外表皮层,在osy突变幼虫中不受影响。这与Snu的功能形成对比,Snu是另一种构造表皮向内和向外屏障所需的ABC转运蛋白,但它与CHC沉积有关。因此,Osy和Snu具有重叠和独立的作用,以建立针对蒸腾和异源生物渗透的表皮抵抗力。osy缺陷表型与人类abca12基因突变引起的丑角鱼鳞病的表型相似。因此,似乎在进化过程中,皮肤中脂质屏障组装的细胞和分子机制是保守的。
更新日期:2020-02-18
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