Department of Life Science, College of Science, Rikkyo University, Toshima-ku, Tokyo 171-8501, Japan
Department of Life Science, College of Science, Rikkyo University, Toshima-ku, Tokyo 171-8501, Japan.
J Cell Sci. 2020 Mar 26;133(6):jcs238527. doi: 10.1242/jcs.238527.
Membrane lipid biosynthesis is a complex process that occurs in various intracellular compartments. In , 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 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 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.
膜脂生物合成是一个发生在各种细胞内隔室的复杂过程。在 ，催化糖基磷脂酰肌醇（GPI）中第三个甘露糖添加的磷脂酰肌醇聚糖-B（PIG-B）定位于核膜（NE）。尽管这种 NE 定位对于 发育是必不可少的，但潜在的分子机制仍不清楚。为了阐明这一机制，我们通过进行免疫沉淀和蛋白质组学分析来鉴定 PIG-B 相互作用蛋白。然后，我们检查了这些蛋白质中的哪些对于 PIG-B 的 NE 定位是必需的。B 型核纤层蛋白 Lamin Dm0 的敲低导致 PIG-B 从 NE 错误定位到内质网。Lamin Dm0 与核内膜上的 PIG-B 结合，这一过程需要 Lamin Dm0 的尾部结构域。此外，在 突变体中 GPI 部分分布异常。这些数据表明 Lamin Dm0 参与 PIG-B 的 NE 定位，并且是蛋白质正确的 GPI-锚修饰所必需的。
