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Regulation of Notch signaling and endocytosis by the Lgl neoplastic tumor suppressor
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posted on 2022-03-23, 05:49 authored by Marta Portela-EstebanMarta Portela-Esteban, LM Parsons, NA Grzeschik, Helena RichardsonHelena RichardsonThe 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.
Funding
HER is supported by a Senior Research Fellowship from the National Health and Medical Research Council, Australia. This work was supported by grants from the Cancer Council Victoria #APP1041817 to HER and CASS Foundation #SM/13/4847 to LMP.
History
Publication Date
2015-07-01Journal
Cell CycleVolume
14Issue
10Pagination
11p. (p. 1496-1506)Publisher
Taylor and FrancisISSN
1538-4101Rights Statement
© 2015 Taylor and Francis. All rights reserved.Publisher DOI
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