Abstract:
:Integrin-containing focal adhesions transmit extracellular signals across the plasma membrane to modulate cell adhesion, signalling and survival. Although integrins are known to undergo continuous endo/exocytic traffic, the potential impact of endocytic traffic on integrin-induced signals is unknown. Here, we demonstrate that integrin signalling is not restricted to cell-ECM adhesions and identify an endosomal signalling platform that supports integrin signalling away from the plasma membrane. We show that active focal adhesion kinase (FAK), an established marker of integrin-ECM downstream signalling, localizes with active integrins on endosomes. Integrin endocytosis positively regulates adhesion-induced FAK activation, which is early endosome antigen-1 and small GTPase Rab21 dependent. FAK binds directly to purified endosomes and becomes activated on them, suggesting a role for endocytosis in enhancing distinct integrin downstream signalling events. Finally, endosomal integrin signalling contributes to cancer-related processes such as anoikis resistance, anchorage independence and metastasis.
journal_name
Nat Cell Bioljournal_title
Nature cell biologyauthors
Alanko J,Mai A,Jacquemet G,Schauer K,Kaukonen R,Saari M,Goud B,Ivaska Jdoi
10.1038/ncb3250subject
Has Abstractpub_date
2015-11-01 00:00:00pages
1412-21issue
11eissn
1465-7392issn
1476-4679pii
ncb3250journal_volume
17pub_type
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