Phospholipid membrane composition affects EGF receptor and Notch signaling through effects on endocytosis during Drosophila development.
The role of phospholipids in the regulation of membrane trafficking and signaling is largely unknown. Phosphatidylcholine (PC) is a main component of the plasma membrane. Mutants in the Drosophila phosphocholine cytidylyltransferase 1 (CCT1), the rate-limiting enzyme in PC biosynthesis, show an altered phospholipid composition with reduced PC and increased phosphatidylinositol (PI) levels. Phenotypic features of dCCT1 indicate that the enzyme is not required for cell survival, but serves a role in endocytic regulation. CCT1- cells show an increase in endocytosis and enlarged endosomal compartments, whereas lysosomal delivery is unchanged. As a consequence, an increase in endocytic localization of EGF receptor (Egfr) and Notch is observed, and this correlates with a reduction in signaling strength and leads to patterning defects. A further link between PC/PI content, endocytosis, and signaling is supported by genetic interactions of dCCT1 with Egfr, Notch, and genes affecting endosomal traffic.
Weber
Ursula
U
Brookdale Department of Molecular, Cell, and Developmental Biology, Mount Sinai School of Medicine, New York, NY 10029, USA.
Eroglu
Cagla
C
Mlodzik
Marek
M
D000818:Animals; D030801:Animals, Genetically Modified; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D002470:Cell Survival; D002855:Chromatography, Thin Layer; D002966:Clathrin / Q000378:metabolism; D003001:Cloning, Molecular; D003034:Coated Pits, Cell-Membrane / Q000648:ultrastructure; D004330:Drosophila / Q000254:growth & development*; D029721:Drosophila Proteins; D004705:Endocytosis / Q000502:physiology*; D066246:ErbB Receptors / Q000502:physiology*; D005124:Eye Abnormalities / Q000235:genetics / Q000648:ultrastructure; D006360:Heat-Shock Proteins / Q000235:genetics; D007150:Immunohistochemistry; D019476:Insect Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000502:physiology*; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D018832:Molecular Chaperones / Q000235:genetics; D009154:Mutation; D010641:Phenotype; D010743:Phospholipids / Q000737:chemistry / Q000502:physiology*; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D051880:Receptors, Notch; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000502:physiology*; D013347:Subcellular Fractions / Q000378:metabolism; D019076:Transgenes
D002966:Clathrin; D029721:Drosophila Proteins; D006360:Heat-Shock Proteins; D019476:Insect Proteins; D008565:Membrane Proteins; D018832:Molecular Chaperones; C497759:N protein, Drosophila; D010743:Phospholipids; D051880:Receptors, Notch; D066246:ErbB Receptors