Nuclear envelope localization of PIG-B is essential for GPI-anchor synthesis in Drosophila.
Nuclear envelope localization of PIG-B is essential for GPI-anchor synthesis in Drosophila.
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DOI：
10.1242/jcs.218024
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发表时间：
2018-10-26
影响因子：
4
通讯作者：
Goto S
中科院分区：
文献类型：
--
作者：
Yamamoto-Hino M;Katsumata E;Suzuki E;Maeda Y;Kinoshita T;Goto S
膜脂质生物合成是一个复杂的过程，发生在各种细胞内区室。糖基磷脂酰肌醇（GPI）是一种参与某些蛋白质膜锚定的脂质，由PIG酶合成。大多数PIGs定位于内质网（ER），但果蝇PIG-B（DmPIG-B）定位于核膜（NE）。为了确定DmPIG-B的NE定位是否在功能上重要，我们定义了定位的决定因素并生成了ER定位形式，表示为DmPIG-B[ER]。DmPIG-B[ER]的酶活性与NE定位的DmPIG-B[NE]的酶活性相当。DmPIG-B[ER]的表达未能有效地挽救PIG-B突变体的致死性，而DmPIG-B[NE]则完全挽救了这种致死性。DmPIG-B[ER]优先被溶酶体降解，这表明NE定位对于蛋白质的功能和稳定性至关重要。此外，我们发现ER靠近NE的区域是GPI锚定蛋白的翻译和GPI添加的位点。因此，NE和近端ER可以提供用于有效GPI锚定的平台。总结：在果蝇中，酶PIG-B在核膜（NE）中的定位对于GPI锚合成是重要的，并且NE和核周ER形成GPI修饰的平台。
Membrane lipid biosynthesis is a complex process that takes place in various intracellular compartments. Glycosylphosphatidylinositol (GPI), a lipid involved in membrane anchoring of some proteins, is synthesized by the PIG enzymes. Most PIGs are localized to the endoplasmic reticulum (ER), but Drosophila PIG-B (DmPIG-B) is localized to the nuclear envelope (NE). To determine whether the NE localization of DmPIG-B is functionally important, we defined the determinants of localization and generated an ER-localized form, denoted DmPIG-B[ER]. The enzymatic activity of DmPIG-B[ER] was comparable to that of NE-localized DmPIG-B[NE]. Expression of DmPIG-B[ER] inefficiently rescued the lethality of the PIG-B mutant, whereas DmPIG-B[NE] rescued this lethality fully. DmPIG-B[ER] was preferentially degraded by lysosomes, suggesting that the NE localization is essential for function and stability of the protein. In addition, we found that the region of the ER proximal to the NE is the site of translation of GPI-anchored proteins and addition of GPI. Thus, the NE and proximal ER may provide a platform for efficient GPI anchoring. Summary: In Drosophila, localization of the enzyme PIG-B in the nuclear envelope (NE) is important for GPI anchor synthesis, and the NE and the perinuclear ER form a platform for the GPI modification.
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影响因子：
64.5
作者：
Muñiz, M;Morsomme, P;Riezman, H
通讯作者：
Riezman, H
影响因子：
4.8
作者：
Nakamura, N;Inoue, N;Kinoshita, T
通讯作者：
Kinoshita, T
影响因子：
4.6
作者：
Tanaka, Tsubasa;Nakamura, Akira
通讯作者：
Nakamura, Akira
影响因子：
7.5
作者：
Barton LJ;Soshnev AA;Geyer PK
通讯作者：
Geyer PK
DOI：
10.2183/pjab.90.130
发表时间：
2014
期刊：
Proceedings of the Japan Academy. Series B, Physical and biological sciences
影响因子：
--
作者：
Kinoshita T
通讯作者：
Kinoshita T