Burnett Camilla, Howard Ken
MRC Laboratory for Molecular Cell Biology, and Department of Physiology, University College London, UK.
EMBO Rep. 2003 Aug;4(8):793-9. doi: 10.1038/sj.embor.embor900. Epub 2003 Jul 11.
Wunen (Wun), a homologue of a lipid phosphate phosphatase (LPP), has a crucial function in the migration and survival of primordial germ cells (PGCs) during Drosophila embryogenesis. Past work has indicated that the LPP isoforms may show functional redundancy in certain systems, and that they have broad-range lipid phosphatase activities in vitro, with little apparent specificity between them. We show here that there are marked differences in biochemical activity between fly Wun and mammalian LPPs, with Wun having a narrower activity range than has been reported for the mammalian LPPs. Furthermore, although it is active on a range of substrates in vitro, mouse Lpp1 has no activity on an endogenous Drosophila germ-cell-specific factor in vivo. Conversely, human LPP3 is active, resulting in aberrant migration and PGC death. These results show an absolute difference in bioactivity among LPP isoforms for the first time in a model organism and may point towards an underlying signalling system that is conserved between flies and humans.
Wunen(Wun)是脂质磷酸酶(LPP)的同源物,在果蝇胚胎发育过程中,对原始生殖细胞(PGC)的迁移和存活起着关键作用。过去的研究表明,LPP亚型在某些系统中可能表现出功能冗余,并且它们在体外具有广泛的脂质磷酸酶活性,彼此之间几乎没有明显的特异性。我们在此表明,果蝇Wun和哺乳动物LPPs在生化活性上存在显著差异,Wun的活性范围比报道的哺乳动物LPPs更窄。此外,尽管小鼠Lpp1在体外对一系列底物具有活性,但在体内对果蝇生殖细胞特异性内源性因子却没有活性。相反,人LPP3具有活性,会导致异常迁移和PGC死亡。这些结果首次在模式生物中显示了LPP亚型之间生物活性的绝对差异,可能指向果蝇和人类之间保守的潜在信号系统。