Ubiquitination of alpha 5 beta 1 lntegrin Controls Fibroblast Migration through Lysosomal Degradation of Fibronectin-lntegrin Complexes

作者：Lobert Viola Helene; Brech Andreas; Pedersen Nina Marie; Wesche Jorgen; Oppelt Angela; Malerod Lene; Stenmark Harald^*

来源：Developmental Cell, 2010, 19(1): 148-159.

DOI：10.1016/j.devcel.2010.06.010

• CELLBIO

Cell migration requires endocytosis and recycling of integrins, but it is not known whether degradation of these membrane proteins is involved. Here we demonstrate that in migrating cells, a fraction of the endocytosed fibronectin receptor, alpha 5 beta 1 integrin, is sorted into multivesicular endosomes together with fibronectin and degraded in lysosomes. This sorting requires fibronectin-induced ubiquitination of the alpha 5 subunit, and the activity of the endosomal sorting complex required for transport (ESCRT) machinery, which interacts with alpha 5 beta 1 integrin. Importantly, we demonstrate that both alpha 5 ubiquitination and ESCRT functions are required for proper migration of fibroblasts. We propose that ligand-mediated degradation of alpha 5 beta 1 integrin via the ESCRT pathway is required in order to prevent endosomal accumulation of ligand-bound integrins that might otherwise form nonproductive adhesion sites. Fibronectin and alpha 5 beta 1 integrin therefore are trafficked to lysosomes in a similar way to growth factors and their receptors.

• 出版日期2010-7-20