The membrane-cytoplasm interface of integrin alpha subunits is critical for receptor latency.
Localization of integrin receptors to focal contact sites occurs upon ligand binding. This activity is latent, since unoccupied integrin receptors do not localize to focal contacts. Deletion analysis has revealed that the alpha cytoplasmic domains is required for the maintenance of integrin receptor latency. Our current hypothesis for the mechanism of integrin post-ligand binding events is that there is a change in relationship of alpha and beta cytoplasmic domains, which overcomes receptor latency. One possible mechanism for such a change would involve the amino acid residues at the membrane-cytoplasm interface. To test this hypothesis, we have produced point mutations in the human integrin alpha 1 subunit. These mutations had no effect on the adhesion via alpha 1 beta 1 to its ligand, collagen IV. However, receptor latency is lost in one of these mutants, leading to constitutive focal contact localization. This effect did not occur in receptors with an exchange of intracellular domains, suggesting that the mechanism of loss of latency involves a relative motion of the integrin chains. These results suggest a model in which post-ligand binding events in integrin receptors are associated with changes in the position of the alpha and beta cytoplasmic domains.
Department of Pathology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
R
R
Briesewitz
A
A
Kern
L B
LB
Smilenov
F S
FS
David
E E
EE
Marcantonio
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D002448:Cell Adhesion; D002462:Cell Membrane; D003593:Cytoplasm; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D039423:Integrin alpha1; D016023:Integrins / Q000235:genetics / Q000378:metabolism; D008024:Ligands; D051379:Mice; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D017354:Point Mutation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D038981:Receptors, Collagen; D013329:Structure-Activity Relationship; D019076:Transgenes
D015703:Antigens, CD; D039423:Integrin alpha1; D016023:Integrins; D008024:Ligands; D038981:Receptors, Collagen