AMPK negatively regulates tensin-dependent integrin activity.

A1 Originalartikel i en vetenskaplig tidskrift (referentgranskad)


Interna författare/redaktörer


Publikationens författare: Georgiadou, Lilja, Jacquemet, Guzmán, Rafaeva, Alibert, Yan, Sahgal, Lerche, Manneville, Mäkelä, Ivaska
Publiceringsår: 2017
Tidskrift: Journal of Cell Biology
Tidskriftsakronym: J Cell Biol
Volym: 216
Nummer: 4
Artikelns första sida, sidnummer: 1107
Artikelns sista sida, sidnummer: 1121
ISSN: 1540-8140


Abstrakt

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 β1-integrin inhibitor in fibroblasts. Loss of AMPK promotes β1-integrin activity, the formation of centrally located active β1-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 β1-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 β1-integrins, supporting their activity and promoting fibrillar adhesion formation and integrin-dependent processes.

Senast uppdaterad 2019-23-11 vid 02:52