Fly and mammalian lipid phosphate phosphatase isoforms differ in activity both in vitro and in vivo.
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.
Burnett
Camilla
C
MRC Laboratory for Molecular Cell Biology, and Department of Physiology, University College London, UK.
Howard
Ken
K
D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D002465:Cell Movement; D002478:Cells, Cultured; D002518:Ceramides / Q000378:metabolism; D004330:Drosophila; D029721:Drosophila Proteins / Q000737:chemistry / Q000378:metabolism*; D005854:Germ Cells / Q000502:physiology; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D008246:Lysophospholipids / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D010711:Phosphatidate Phosphatase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010712:Phosphatidic Acids / Q000378:metabolism; D011487:Protein Conformation; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013045:Species Specificity; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism; D013379:Substrate Specificity
D002518:Ceramides; D029721:Drosophila Proteins; D007527:Isoenzymes; D008246:Lysophospholipids; D008565:Membrane Proteins; D010712:Phosphatidic Acids; D011993:Recombinant Fusion Proteins; C065576:ceramide 1-phosphate; C060506:sphingosine 1-phosphate; C112948:lipid phosphate phosphatase; D010711:Phosphatidate Phosphatase; C103065:wun protein, Drosophila; D013110:Sphingosine