title: Regulation of Notch signaling and endocytosis by the Lgl neoplastic tumor suppressor.
abstract: The evolutionarily conserved neoplastic tumor suppressor protein, Lethal (2) giant larvae (Lgl), plays roles in cell polarity and tissue growth via regulation of the Hippo pathway. In our recent study, we showed that in the developing Drosophila eye epithelium, depletion of Lgl leads to increased ligand-dependent Notch signaling. lgl mutant tissue also exhibits an accumulation of early endosomes, recycling endosomes, early-multivesicular body markers and acidic vesicles. We showed that elevated Notch signaling in lgl(-) tissue can be rescued by feeding larvae the vesicle de-acidifying drug chloroquine, revealing that Lgl attenuates Notch signaling by limiting vesicle acidification. Strikingly, chloroquine also rescued the lgl(-) overgrowth phenotype, suggesting that the Hippo pathway defects were also rescued. In this extraview, we provide additional data on the regulation of Notch signaling and endocytosis by Lgl, and discuss possible mechanisms by which Lgl depletion contributes to signaling pathway defects and tumorigenesis.
authors: a Cell Cycle and Development Laboratory; Research Division ; Peter MacCallum Cancer Centre ; Melbourne , Victoria , Australia.
authors: Marta
authors: M
authors: Portela
authors: Linda M
authors: LM
authors: Parsons
authors: Nicola A
authors: NA
authors: Grzeschik
authors: Helena E
authors: HE
authors: Richardson
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects; D016764:Cell Polarity; D002738:Chloroquine / Q000494:pharmacology; D004330:Drosophila / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004705:Endocytosis; D056827:Endosomal Sorting Complexes Required for Transport / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism; D005123:Eye / Q000378:metabolism / Q000473:pathology; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D018613:Microscopy, Confocal; D009154:Mutation; D010641:Phenotype; D011493:Protein Kinase C / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D020691:rab GTP-Binding Proteins / Q000378:metabolism; D000090802:rab7 GTP-Binding Proteins; D000099317:Hippo Kinases
chemical_list: D002738:Chloroquine; D029721:Drosophila Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D047908:Intracellular Signaling Peptides and Proteins; D011493:Protein Kinase C; D017346:Protein Serine-Threonine Kinases; D051880:Receptors, Notch; D025521:Tumor Suppressor Proteins; D020691:rab GTP-Binding Proteins; D000090802:rab7 GTP-Binding Proteins; C497759:N protein, Drosophila; C511665:Vps25 protein, Drosophila; C499474:hpo protein, Drosophila; D000099317:Hippo Kinases
keywords: Drosophila; Hippo; Lgl, Lethal (2) giant larvae; Notch; aPKC, atypical Protein Kinase C; chloroquine; endocytosis; lgl