Drosophila GPI-mannosyltransferase 2 is required for GPI anchor attachment and surface expression of chaoptin.
Drosophila GPI-mannosyltransferase 2 is required for GPI anchor attachment and surface expression of chaoptin.
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DOI：
10.1017/s0952523812000181
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发表时间：
2012-05
影响因子：
1.9
通讯作者：
Colley, Nansi Jo
中科院分区：
文献类型：
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作者：
Rosenbaum, Erica E.;Brehm, Kimberley S.;Vasiljevic, Eva;Gajeski, Allen;Colley, Nansi Jo
关键词：
糖基磷脂酰肌醇（GPI）锚点对于多种必需的信号和细胞粘附蛋白的膜附着至关重要。GPI锚点是一种复杂的糖脂结构，利用糖基磷脂酰肌醇-甘露糖基转移酶（GPI- mt）在其生物合成过程中添加三个核心甘露糖残基。在这里，我们证明了果蝇GPI-MT2是gpi介导的几种gpi锚定蛋白（包括光受体特异性细胞粘附分子chaoptin）的膜附着所必需的。gpi-mt2的突变导致果蝇光感受器细胞向质膜运输chaoptin的缺陷。在gpi-mt2突变体中，膜中足够的chaoptin的丢失导致微绒毛不稳定、光感受器细胞病理和视网膜变性。最后，利用定点诱变技术，我们确定了果蝇GPI-MT2功能和细胞活力所必需的关键氨基酸。我们关于GPI- mt2的发现提供了果蝇GPI锚定生物合成和蛋白质运输之间的机制联系，并揭示了遗传性视网膜变性的新机制。
Glycosylphosphatidylinositol (GPI) anchors are critical for the membrane attachment of a wide variety of essential signaling and cell adhesion proteins. The GPI anchor is a complex glycolipid structure that utilizes glycosylphosphatidylinositol-mannosyltransferases (GPI-MTs) for the addition of three core mannose residues during its biosynthesis. Here, we demonstrate that Drosophila GPI-MT2 is required for the GPI-mediated membrane attachment of several GPI-anchored proteins, including the photoreceptor-specific cell adhesion molecule, chaoptin. Mutations in gpi-mt2 lead to defects in chaoptin trafficking to the plasma membrane in Drosophila photoreceptor cells. In gpi-mt2 mutants, loss of sufficient chaoptin in the membrane leads to microvillar instability, photoreceptor cell pathology, and retinal degeneration. Finally, using site-directed mutagenesis, we have identified key amino acids that are essential for GPI-MT2 function and cell viability in Drosophila. Our findings on GPI-MT2 provide a mechanistic link between GPI anchor biosynthesis and protein trafficking in Drosophila and shed light on a novel mechanism for inherited retinal degeneration.