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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Abnormal phagocytosis by retinal pigmented epithelium that lacks myosin Vila, the Usher syndrome 1B protein
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Abnormal phagocytosis by retinal pigmented epithelium that lacks myosin Vila, the Usher syndrome 1B protein

机译：缺乏肌球蛋白维拉（Usher综合征1B蛋白）的视网膜色素上皮细胞的异常吞噬作用

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摘要

Mutations in the myosin Vila gene (MYO7A) cause Usher syndrome type 1B (USH1B), a major type of the deaf-blind disorder, Usher syndrome. We have studied mutant phenotypes in the retinas of Myo7a mutant mice (shaker1), with the aim of elucidating the role(s) of myosin Vila in the retina and what might underlie photoreceptor degeneration in USH1B patients. A photoreceptor defect has been described. Here, we report that the phagocytosis of photoreceptor outer segment disks by the retinal pigment epithelium (RPE) is abnormal in Myo7a null mice. Both in vivo and in primary cultures of RPE cells, the transport of ingested disks out of the apical region is inhibited in the absence of Myo7a. The results with the cultured RIPE cells were the same, irrespective of whether the disks came from wild-type or mutant mice, thus demonstrating that the RPE is the source of this defect. The inhibited transport seems to delay phagosome-lysosomal fusion, as the degradation of ingested disks was slower in mutant RPE. Moreover, fewer packets of disk membranes were ingested in vivo, possibly because retarded removal of phagosomes from the apical processes inhibited the ingestion of additional disk membranes. We conclude that Myo7a is required for the normal processing of ingested disk membranes in the RPE, primarily in the basal transport of phagosomes into the cell body where they then fuse with lysosomes. Because the phagocytosis of photoreceptor disks by the RPE has been shown to be critical for photoreceptor cell viability, this defect likely contributes to the progressive blindness in USH1B. [References: 54]
机译：肌球蛋白Vila基因（MYO7A）中的突变会引起1B型Usher综合征（USH1B），这是聋盲症的一种主要类型，Usher综合征。我们已经研究了Myo7a突变小鼠（shaker1）的视网膜中的突变表型，目的是阐明肌球蛋白Vila在视网膜中的作用以及在USH1B患者中可能是光感受器变性的基础。已经描述了感光体缺陷。在这里，我们报告说，视网膜色素上皮（RPE）的感光细胞外段盘的吞噬作用在Myo7a缺失小鼠中是异常的。无论在体内还是在RPE细胞的原代培养中，在没有Myo7a的情况下，摄入的椎间盘从根尖区的运输都受到抑制。无论圆盘是来自野生型小鼠还是突变型小鼠，培养的RIPE细胞的结果都是相同的，从而证明RPE是此缺陷的来源。抑制的运输似乎延迟了吞噬体-溶酶体融合，因为在突变的RPE中摄入的盘的降解较慢。而且，体内摄入的圆盘膜包减少了，这可能是因为吞噬体从根尖过程中的去除延迟抑制了其他圆盘膜的摄入。我们得出结论，Ryo摄取圆盘膜的正常加工需要Myo7a，主要是吞噬体向细胞体内的基础转运，然后吞噬体与溶酶体融合。由于已显示RPE吞噬感光体盘对感光细胞的生存能力至关重要，因此该缺陷可能导致USH1B的进行性失明。 [参考：54]

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