Lamin is essential for nuclear localization of the GPI synthesis enzyme PIG-B and GPI-anchored protein production in Drosophila
Lamin is essential for nuclear localization of the GPI synthesis enzyme PIG-B and GPI-anchored protein production in Drosophila
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DOI：
10.1242/jcs.238527
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发表时间：
2020-02
影响因子：
4
通讯作者：
M. Yamamoto-Hino;K. Kawaguchi;M. Ono;K. Furukawa;S. Goto
中科院分区：
文献类型：
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作者：
M. Yamamoto-Hino;K. Kawaguchi;M. Ono;K. Furukawa;S. Goto
膜脂生物合成是一个复杂的过程，发生在不同的细胞内。在果蝇中，催化糖基磷脂酰肌醇（GPI）中第三甘露糖加成的磷脂酰肌醇聚糖- b （PIG-B）定位于核膜（NE）。尽管这种NE定位对果蝇的发育至关重要，但其潜在的分子机制尚不清楚。为了阐明这一机制，我们通过免疫沉淀和蛋白质组学分析鉴定了猪- b相互作用蛋白。然后，我们检查了这些蛋白质中哪些是猪- b的NE定位所必需的。Lamin Dm0（一种b型Lamin）的敲低导致猪- b从NE到内质网的错误定位。Lamin Dm0在核膜内与猪- b结合，这一过程需要Lamin Dm0的尾部结构域。此外，GPI部分在Lamin Dm0突变体中分布异常。这些数据表明，Lamin Dm0参与了猪- b的NE定位，并且是正确的gpi锚定蛋白修饰所必需的。Lamin通过将GPI修饰酶PIG-B拴在核膜上，参与质膜蛋白的翻译后修饰。
ABSTRACT Membrane lipid biosynthesis is a complex process that occurs in various intracellular compartments. In Drosophila, phosphatidylinositol glycan-B (PIG-B), which catalyzes addition of the third mannose in glycosylphosphatidylinositol (GPI), localizes to the nuclear envelope (NE). Although this NE localization is essential for Drosophila development, the underlying molecular mechanism remains unknown. To elucidate this mechanism, we identified PIG-B-interacting proteins by performing immunoprecipitation followed by proteomic analysis. We then examined which of these proteins are required for the NE localization of PIG-B. Knockdown of Lamin Dm0, a B-type lamin, led to mislocalization of PIG-B from the NE to the endoplasmic reticulum. Lamin Dm0 associated with PIG-B at the inner nuclear membrane, a process that required the tail domain of Lamin Dm0. Furthermore, GPI moieties were distributed abnormally in the Lamin Dm0 mutant. These data indicate that Lamin Dm0 is involved in the NE localization of PIG-B and is required for proper GPI-anchor modification of proteins. Highlighted Article: Lamin plays a role in post-translational modification of plasma membrane proteins by tethering the GPI modification enzyme PIG-B to the inner nuclear membrane.