Journal article

Lgl reduces endosomal vesicle acidification and Notch signaling by promoting the interaction between Vap33 and the V-ATPase complex

Marta Portela, Liu Yang, Sayantanee Paul, Xia Li, Alexey Veraksa, Linda M Parsons, Helena E Richardson

SCIENCE SIGNALING | AMER ASSOC ADVANCEMENT SCIENCE | Published : 2018

Abstract

Epithelial cell polarity is linked to the control of tissue growth and tumorigenesis. The tumor suppressor and cell polarity protein lethal-2-giant larvae (Lgl) promotes Hippo signaling and inhibits Notch signaling to restrict tissue growth in Drosophila melanogaster Notch signaling is greater in lgl mutant tissue than in wild-type tissue because of increased acidification of endosomal vesicles, which promotes the proteolytic processing and activation of Notch by γ-secretase. We showed that the increased Notch signaling and tissue growth defects of lgl mutant tissue depended on endosomal vesicle acidification mediated by the vacuolar adenosine triphosphatase (V-ATPase). Lgl promoted the acti..

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University of Melbourne Researchers

Grants

Awarded by Cancer Council Victoria grant


Awarded by Juan de la Cierva-Incorporacion postdoctoral fellowship from the Spanish Ministerio de Ciencia e Innovacion


Awarded by National Health and Medical Research Council Fellowship level B


Awarded by NIH



Awarded by EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT


Awarded by NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES


Funding Acknowledgements

The project and M.P. were supported by Cancer Council Victoria grant APP1041817 (to H.E.R. and A.V.), a Juan de la Cierva-Incorporacion postdoctoral fellowship (IJCI-2014-19272) from the Spanish Ministerio de Ciencia e Innovacion (to M.P.), Contributing to Australian Scholarship and Science Foundation grant SM/14/5398 (to L.M.P.), and NIH grants HD085870 and GM123136 (to A.V.). H.E.R. was supported by a National Health and Medical Research Council Fellowship level B (APP1020056), a Bridging Fellowship from La Trobe University, and funds from the La Trobe Institute of Molecular Science.