Summary of project PR000897

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench,, where it has been assigned Project ID PR000897. The data can be accessed directly via it's Project DOI: 10.21228/M8R704 This work is supported by NIH grant, U2C- DK119886.


Project ID: PR000897
Project DOI:doi: 10.21228/M8R704
Project Title:GSK3 inhibits macropinocytosis and lysosomal activity through the Wnt destruction complex machinery
Project Summary:Canonical Wnt signaling is emerging as a major regulator of endocytosis. Here we report that mutation of Axin1, a tumor-suppressor part of the β-catenin destruction complex, results in the activation of macropinocytosis in Alexander hepatocellular carcinoma (HCC) cells. Axin1 binds Glycogen Synthase Kinase 3 (GSK3), and we found that inhibition of GSK3 by Lithium chloride (LiCl), CHIR99021 or dominant-negative GSK3 triggered macropinocytosis. GSK3 inhibition caused a rapid increase in endolysosomes that was independent of new protein synthesis. GSK3 inhibition or Axin1 mutation increased lysosomal activity, which could be followed with tracers for active cathepsin D, β-glucosidase, and ovalbumin degradation. Microinjection of LiCl into the blastula cavity of Xenopus embryos caused a striking increase in dextran macropinocytosis. The effects of GSK3 inhibition on macropinocytosis and protein degradation in endolysosomes were blocked by the macropinocytosis inhibitors EIPA or IPA-2, suggesting that the increased membrane trafficking drives lysosomal activity and nutrient acquisition.
Institute:University of California, Los Angeles
Department:Biological Chemisty
Laboratory:De Robertis Lab
Last Name:De Robertis
First Name:Edward
Address:5-612A MRL
Phone:(310) 206-1401

Summary of all studies in project PR000897

Study IDStudy TitleSpeciesInstituteAnalysis
(* : Contains Untargted data)
(* : Contains raw data)
ST001320 Examination of labeled glucose utilization in central carbon metabolism in HeLa cells post WNT stimulation Homo sapiens University of California, Los Angeles MS 2020-07-18 1 12 Uploaded data (11G)*