Hyccin/FAM126A deficiency reduces glial enrichment and axonal sheath, which are rescued by overexpression of a plasma membrane- targeting PI4KIIIa in Drosophila
Hyccin/FAM126A deficiency reduces glial enrichment and axonal sheath, which are rescued by overexpression of a plasma membrane- targeting PI4KIIIa in Drosophila
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Hyccin/FAM126A 缺乏会减少神经胶质富集和轴突鞘，这是通过果蝇中质膜靶向 PI4KIIIα 的过度表达来挽救的。
DOI：
10.1016/j.bbrc.2021.11.106
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发表时间：
2021-12-08
影响因子：
3.1
通讯作者：
Wang，Wen-An
中科院分区：
文献类型：
--
作者：
Zhang，Qichao;Zhang，Baozhu;Wang，Wen-An
Hyccin/FAM126A突变与髓鞘过少和先天性白内障(HCC)有关，但Hyccin/FAM126A缺乏是否以及如何导致髓鞘过少仍未确定。本研究表明，HYCIN/FAM126A的表达是果蝇表达PI4KIIIα复合体其他成分所必需的。HYCIN/FAM126A在胶质细胞中的敲除减少了神经胶质细胞的浓缩，破坏了视觉系统的轴突和视觉能力，这些缺陷可以通过过表达人FAM126A或FAM126B而完全修复，通过过度表达质膜靶向的重组小鼠PI4KIIIα可以部分修复。此外，PI4KIIIα在胶质细胞表型复制的HYCIN/FAM126A中被击倒，这可以通过过度表达重组的PI4KIIIα而部分挽救，但不表达人FAM126A或FAM126B。本研究建立了一种肝细胞癌动物模型，表明Hycin/FAM126A通过控制PI4KIIIα复合体在质膜上的表达和稳定，以细胞自主的方式在视觉系统中对胶质细胞的丰富和轴索的形成起着重要的作用。
Hyccin/FAM126A mutations are linked to hypomyelination and congenital cataract disease (HCC), but whether and how Hyccin/FAM126A deficiency causes hypomyelination remains undetermined. This study shows Hyccin/FAM126A expression was necessary for the expression of other components of the PI4KIIIα complex inDrosophila. Knockdown of Hyccin/FAM126A in glia reduced the enrichment of glial cells, disrupted axonal sheaths and visual ability in the visual system, and these defects could be fully rescued by overexpressing either human FAM126A or FAM126B, and partially rescued by overexpressing a plasma membrane-targeting recombinant mouse PI4KIIIα. Additionally, PI4KIIIα knockdown in glia phenocopied Hyccin/FAM126A knockdown, and this was partially rescued by overexpressing the recombinant PI4KIIIα, but not human FAM126A or FAM126B. This study establishes an animal model of HCC and indicates that Hyccin/FAM126A plays an essential role in glial enrichment and axonal sheath in a cell-autonomous manner in the visual system via controlling the expression and stabilization of the PI4KIIIα complex at the plasma membrane.