Disruption of focal adhesions by integrin cytoplasmic domain-associated protein-1 alpha.
Regulation of integrin affinity and clustering plays a key role in the control of cell adhesion and migration. The protein ICAP-1 alpha (integrin cytoplasmic domain-associated protein-1 alpha) binds to the cytoplasmic domain of the beta(1A) integrin and controls cell spreading on fibronectin. Here, we demonstrate that, despite its ability to interact with beta(1A) integrin, ICAP-1 alpha is not recruited in focal adhesions, whereas it is colocalized with the integrin at the ruffling edges of the cells. ICAP-1 alpha induced a rapid disruption of focal adhesions, which may result from the ability of ICAP-1 alpha to inhibit the association of beta(1A) integrin with talin, which is crucial for the assembly of these structures. ICAP-1 alpha-mediated dispersion of beta(1A) integrins is not observed with beta(1D) integrins that do not bind ICAP. This strongly suggests that ICAP-1 alpha action depends on a direct interaction between ICAP-1 alpha and the cytoplasmic domain of the beta(1) chains. Altogether, these results suggest that ICAP-1 alpha plays a key role in cell adhesion by acting as a negative regulator of beta(1) integrin avidity.
Bouvard
Daniel
D
Laboratoire d'Etude de la Differenciation et de l'Adhérence Cellulaires, Unité Mixte de Recherche UJF/CNRS 5538, Institut Albert Bonniot, Faculte de Médecine de Grenoble, La Tronche F38706 cedex, France.
Vignoud
Lucile
L
Dupé-Manet
Sandra
S
Abed
Nadia
N
Fournier
Henri-Noël
HN
Vincent-Monegat
Carole
C
Retta
Saverio Francesco
SF
Fassler
Reinhard
R
Block
Marc R
MR
D016475:3T3 Cells; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D016466:CHO Cells; D002352:Carrier Proteins / Q000737:chemistry / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology*; D002465:Cell Movement; D006224:Cricetinae; D003593:Cytoplasm / Q000502:physiology; D022001:Focal Adhesions / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D019012:Integrin beta1 / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins; D007700:Kinetics; D008565:Membrane Proteins; D051379:Mice; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C108257:ITGB1BP1 protein, human; D019012:Integrin beta1; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D011993:Recombinant Fusion Proteins