The conserved c2 domain protein lethal (2) giant discs regulates protein trafficking in Drosophila.
Drosophila sensory organ precursor (SOP) cells undergo several rounds of asymmetric cell division to generate the four different cell types that make up external sensory organs. Establishment of different fates among daughter cells of the SOP relies on differential regulation of the Notch pathway. Here, we identify the protein Lethal (2) giant discs (Lgd) as a critical regulator of Notch signaling in the SOP lineage. We show that lgd encodes a conserved C2 domain protein that binds to phospholipids present on early endosomes. When Lgd function is compromised, Notch and other transmembrane proteins accumulate in enlarged early endosomal compartments. These enlarged endosomes are positive for Rab5 and Hrs, a protein involved in trafficking into the degradative pathway. Our experiments suggest that Lgd is a critical regulator of endocytosis that is not present in yeast and acts in the degradative pathway after Hrs.
Gallagher
Ciara M
CM
Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Dr Bohr Gasse 3, 1030 Vienna, Austria.
Knoblich
Juergen A
JA
D000818:Animals; D002455:Cell Division; D019070:Cell Lineage; D002478:Cells, Cultured; D004330:Drosophila / Q000254:growth & development / Q000378:metabolism / Q000502:physiology*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D056827:Endosomal Sorting Complexes Required for Transport; D011992:Endosomes / Q000378:metabolism; D007814:Larva; D008969:Molecular Sequence Data; D009154:Mutation; D010743:Phospholipids / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D051880:Receptors, Notch / Q000378:metabolism; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000502:physiology*; D020696:rab5 GTP-Binding Proteins / Q000378:metabolism
D029721:Drosophila Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D010743:Phospholipids; D010750:Phosphoproteins; D051880:Receptors, Notch; D025521:Tumor Suppressor Proteins; C096164:hepatocyte growth factor-regulated tyrosine kinase substrate; C515862:l(2)gd1 protein, Drosophila; D020696:rab5 GTP-Binding Proteins