AMP-activated protein kinase fortifies epithelial tight junctions during energetic stress via its effector GIV/Girdin

• DOI: 10.7554/elife.20795
• Publication Date: 2016-11-04T13:00:08Z
• Authors: Nicolas Aznar; Arjun Patel; Cristina C Rohena; Ying Dunkel; Linda P Joosen; Vanessa Taupin; Irina Kufareva; Marilyn G Farquhar; Pradipta Ghosh
• Keywords: Cell polarity; AMP-Activated Protein Kinase; Barrier function

Loss of epithelial polarity impacts organ development and function; it is also oncogenic. AMPK, a key sensor metabolic stress stabilizes cell-cell junctions maintains polarity; its activation by Metformin protects the barrier against suppresses tumorigenesis. How AMPK epithelium remains unknown. Here, we identify GIV/Girdin as novel effector whose phosphorylation at single site both necessary sufficient for strengthening mammalian tight preserving cell function in face energetic stress. Expression an oncogenic mutant GIV (cataloged TCGA) that cannot be phosphorylated increased anchorage-independent growth tumor cells helped these to evade tumor-suppressive action Metformin. This work defines fundamental homeostatic mechanism which AMPK-GIV axis reinforces stress-induced collapse provides mechanistic insight into