The chicken yolk sac IgY receptor, a mammalian mannose receptor family member, transcytoses IgY across polarized epithelial cells
The chicken yolk sac IgY receptor, a mammalian mannose receptor family member, transcytoses IgY across polarized epithelial cells
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DOI：
10.1091/mbc.e07-09-0972
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发表时间：
2008-04-01
影响因子：
3.3
通讯作者：
Bjorkman, Pamela J.
中科院分区：
文献类型：
--
作者：
Tesar, Devin B.;Cheung, Evelyn J.;Bjorkman, Pamela J.
在哺乳动物中，被动免疫从母体向幼体的转移是由MHC相关受体FcRN介导的，FcRN负责将母体的免疫球蛋白穿过上皮细胞屏障。在禽类中，母体卵黄中的卵黄抗体通过卵黄囊转移，在怀孕和早期独立生活中被动免疫雏鸡。鸡卵黄囊IgY受体(FcRY)是哺乳动物磷脂酶A2受体(甘露糖受体家族成员)的同源基因，而不是FcRN或MHC同源基因。FcRN和FcRY在内体的酸性pH下都表现出配体结合，而在血液的微碱性pH下都表现出配体的释放。在这里，我们展示了在极化的哺乳动物上皮细胞中表达的FcRY在鸡FCY/IgY的内吞、双向细胞转运和循环中发挥作用。共聚焦免疫荧光研究表明，IgY结合和内吞作用发生在酸性而不是碱性的pH，类似于FcRN对免疫球蛋白的pH依赖摄取。共定位研究表明，FcRY通过笼蛋白包裹的凹坑和涉及早期和再循环内小体的运输而介导内化。微管的破坏部分地抑制了根尖-基底外侧和基底-外侧-根尖的跨细胞分裂，但不能再循环，这表明使用了不同的运输机制。我们的结果代表了FcRY和FcRN功能等同的第一个细胞生物学证据，并提供了一个有趣的例子，说明进化如何产生利用不同蛋白质折叠满足不同物种相似生物需求的系统。
In mammals the transfer of passive immunity from mother to young is mediated by the MHC-related receptor FcRn, which transports maternal IgG across epithelial cell barriers. In birds, maternal IgY in egg yolk is transferred across the yolk sac to passively immunize chicks during gestation and early independent life. The chicken yolk sac IgY receptor (FcRY) is the ortholog of the mammalian phospholipase A2 receptor, a mannose receptor family member, rather than an FcRn or MHC homolog. FcRn and FcRY both exhibit ligand binding at the acidic pH of endosomes and ligand release at the slightly basic pH of blood. Here we show that FcRY expressed in polarized mammalian epithelial cells functioned in endocytosis, bidirectional transcytosis, and recycling of chicken FcY/IgY. Confocal immunofluorescence studies demonstrated that IgY binding and endocytosis occurred at acidic but not basic pH, mimicking pH-dependent uptake of IgG by FcRn. Colocalization studies showed FcRY-mediated internalization via clathrin-coated pits and transport involving early and recycling endosomes. Disruption of microtubules partially inhibited apical-to-basolateral and basolateral-to-apical transcytosis, but not recycling, suggesting the use of different trafficking machinery. Our results represent the first cell biological evidence of functional equivalence between FcRY and FcRn and provide an intriguing example of how evolution can give rise to systems in which similar biological requirements in different species are satisfied utilizing distinct protein folds.