Summary of project PR000897
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, 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.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| 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 |
| Email: | ederobertis@mednet.ucla.edu |
| Phone: | (310) 206-1401 |
Summary of all studies in project PR000897
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : 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)* |
