AMP-activated protein kinase fortifies epithelial tight junctions during energetic stress via its effector GIV/Girdin
| Autor: | Cristina C. Rohena, Pradipta Ghosh, Linda P. Joosen, Marilyn G. Farquhar, Vanessa Taupin, Irina Kufareva, Ying Dunkel, Nicolas Aznar, Arjun Patel |
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| Přispěvatelé: | University of California [San Diego] (UC San Diego), University of California |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
AMPK
0301 basic medicine tight junctions [SDV]Life Sciences [q-bio] Vesicular Transport Proteins AMP-Activated Protein Kinases Cell junction AMP-activated protein kinase cell biology Cell polarity Phosphorylation Biology (General) Barrier function ComputingMilieux_MISCELLANEOUS cancer biology Cancer Epithelial polarity Cancer Biology Tight junction biology Chemistry Effector General Neuroscience Microfilament Proteins General Medicine Metformin Cell biology Colon cancer Biochemistry Medicine Research Article Human Metformin AMPK energetic stress ccdc88a/GIRDIN QH301-705.5 Science General Biochemistry Genetics and Molecular Biology Cell Line 03 medical and health sciences Animals Humans human Protein Processing General Immunology and Microbiology epithelial cell polarity Post-Translational Cell Biology 030104 developmental biology biology.protein Generic health relevance Biochemistry and Cell Biology Other Protein Processing Post-Translational |
| Zdroj: | eLife eLife, eLife Sciences Publication, 2016, 5, ⟨10.7554/eLife.20795⟩ eLife, Vol 5 (2016) |
| ISSN: | 2050-084X |
| DOI: | 10.7554/eLife.20795⟩ |
| Popis: | Loss of epithelial polarity impacts organ development and function; it is also oncogenic. AMPK, a key sensor of metabolic stress stabilizes cell-cell junctions and maintains epithelial polarity; its activation by Metformin protects the epithelial barrier against stress and suppresses tumorigenesis. How AMPK protects the epithelium remains unknown. Here, we identify GIV/Girdin as a novel effector of AMPK, whose phosphorylation at a single site is both necessary and sufficient for strengthening mammalian epithelial tight junctions and preserving cell polarity and barrier function in the face of energetic stress. Expression of an oncogenic mutant of GIV (cataloged in TCGA) that cannot be phosphorylated by AMPK increased anchorage-independent growth of tumor cells and helped these cells to evade the tumor-suppressive action of Metformin. This work defines a fundamental homeostatic mechanism by which the AMPK-GIV axis reinforces cell junctions against stress-induced collapse and also provides mechanistic insight into the tumor-suppressive action of Metformin. DOI: http://dx.doi.org/10.7554/eLife.20795.001 |
| Databáze: | OpenAIRE |
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