A1 Journal article – refereed

AMPK negatively regulates tensin-dependent integrin activity




List of Authors: Georgiadou M, Lilja J, Jacquemet G, Guzman C, Rafaeva M, Alibert C, Yan Y, Sahgal P, Lerche M, Manneville JB, Makela TP, Ivaska J

Publisher: ROCKEFELLER UNIV PRESS

Publication year: 2017

Journal: Journal of Cell Biology

Journal name in source: JOURNAL OF CELL BIOLOGY

Journal acronym: J CELL BIOL

Volume number: 216

Issue number: 4

Number of pages: 15

ISSN: 0021-9525

DOI: http://dx.doi.org/10.1083/jcb.201609066


Abstract
Tight regulation of integrin activity is paramount for dynamic cellular functions such as cell matrix adhesion and mechanotransduction. Integrin activation is achieved through intracellular interactions at the integrin cytoplasmic tails and through integrin-ligand binding. In this study, we identify the metabolic sensor AMP-activated protein kinase (AMPK) as a beta 1-integrin inhibitor in fibroblasts. Loss of AMPK promotes beta 1-integrin activity, the formation of centrally located active beta 1-integrin- and tensin-rich mature fibrillar adhesions, and cell spreading. Moreover, in the absence of AMPK, cells generate more mechanical stress and increase fibronectin fibrillogenesis. Mechanistically, we show that AMPK negatively regulates the expression of the integrin-binding proteins tensin1 and tensin3. Transient expression of tensins increases beta 1-integrin activity, whereas tensin silencing reduces integrin activity in fibroblasts lacking AMPK. Accordingly, tensin silencing in AMPK-depleted fibroblasts impedes enhanced cell spreading, traction stress, and fibronectin fiber formation. Collectively, we show that the loss of AMPK up-regulates tensins, which bind beta 1-integrins, supporting their activity and promoting fibrillar adhesion formation and integrin-dependent processes.


Last updated on 2021-24-06 at 09:12