Abstract:
:Integrins are heterodimeric cell-surface adhesion molecules comprising one of 18 possible α-chains and one of eight possible β-chains. They control a range of cell functions in a matrix- and ligand-specific manner. Integrins can be internalized by clathrin-mediated endocytosis (CME) through β subunit-based motifs found in all integrin heterodimers. However, whether specific integrin heterodimers can be selectively endocytosed was unknown. Here, we found that a subset of α subunits contain an evolutionarily conserved and functional YxxΦ motif directing integrins to selective internalization by the most abundant endocytic clathrin adaptor, AP2. We determined the structure of the human integrin α4-tail motif in complex with the AP2 C-μ2 subunit and confirmed the interaction by isothermal titration calorimetry. Mutagenesis of the motif impaired selective heterodimer endocytosis and attenuated integrin-mediated cell migration. We propose that integrins evolved to enable selective integrin-receptor turnover in response to changing matrix conditions.
journal_name
Nat Struct Mol Bioljournal_title
Nature structural & molecular biologyauthors
De Franceschi N,Arjonen A,Elkhatib N,Denessiouk K,Wrobel AG,Wilson TA,Pouwels J,Montagnac G,Owen DJ,Ivaska Jdoi
10.1038/nsmb.3161subject
Has Abstractpub_date
2016-02-01 00:00:00pages
172-9issue
2eissn
1545-9993issn
1545-9985pii
nsmb.3161journal_volume
23pub_type
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