Zhang Weiying, Li Yaqi, Chen Jing, Yao Likun, Zhang Bingjie, Zhang Lin, Liu Boqi, Shen Weimin, Meng Anming, Wu Xiaotong
Laboratory of Molecular Developmental Biology, State Key Laboratory of Membrane Biology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
China West China Hospital, Sichuan University, Chengdu 610044, China.
J Mol Cell Biol. 2025 Jun 12;16(12). doi: 10.1093/jmcb/mjae058.
Proteins without transmembrane domains could be anchored to the cell surface for regulating various biological processes when covalently linked to glycosylphosphatidylinositol (GPI) molecules by the GPI transamidase (GPIT) complex. However, it remains poorly understood whether and how the GPIT complex affects primordial germ cell (PGC) development. In this study, we report the important roles of the GPIT complex in PGC migration and development in zebrafish embryos. Mutation of pigu or pigk, both encoding essential GPIT complex subunits, resulted in defective PGC migration with ectopically located PGCs and reduction of PGC counts. Notably, a detailed analysis of filopodia in PGCs revealed the attenuated polarity of filopodia distribution along the migration direction in mutant embryos. PGC transplantation and PGC-specific rescue experiments demonstrated that both PGC and somatic cell-expressed Pigu are required for PGC migration. Furthermore, expression levels of PGC-specific genes decreased in pigu mutant PGCs with the derepression of somatic cell genes. Hence, we propose that the GPIT complex plays a critical role during PGC migration and development.
没有跨膜结构域的蛋白质在通过糖基磷脂酰肌醇(GPI)转酰胺酶(GPIT)复合物与GPI分子共价连接时,可以锚定在细胞表面以调节各种生物过程。然而,GPIT复合物是否以及如何影响原始生殖细胞(PGC)的发育仍知之甚少。在本研究中,我们报道了GPIT复合物在斑马鱼胚胎PGC迁移和发育中的重要作用。编码必需GPIT复合物亚基的pigu或pigk发生突变,导致PGC迁移缺陷,PGC异位定位且数量减少。值得注意的是,对PGC中丝状伪足的详细分析显示,突变胚胎中丝状伪足沿迁移方向的分布极性减弱。PGC移植和PGC特异性拯救实验表明,PGC迁移需要PGC和体细胞表达的Pigu。此外,在pigu突变的PGC中,PGC特异性基因的表达水平下降,而体细胞基因则去抑制。因此,我们认为GPIT复合物在PGC迁移和发育过程中起关键作用。