Ubiquitination of alpha 5 beta 1 integrin controls fibroblast migration through lysosomal degradation of fibronectin-integrin complexes.

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.
Mesh Terms:
Base Sequence, Cell Movement, Cells, Cultured, Endosomal Sorting Complexes Required for Transport, Endosomes, Fibroblasts, Fibronectins, Green Fluorescent Proteins, Humans, Integrin alpha5beta1, Lysosomes, Microscopy, Immunoelectron, Protein Binding, RNA, Small Interfering, Recombinant Fusion Proteins, Transfection, Ubiquitination
Dev. Cell
Date: Jul. 20, 2010
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