Distinct roles for the alpha and beta subunits in the functions of integrin alphaMbeta2.
Integrin alphaMbeta2 (Mac-1, CD11b/CD18) is a noncovalently linked heterodimer of alphaM and beta2 subunits on the surface of leukocytes, where it plays a pivotal role in the adhesion and migration of these cells. Using HEK293 cells expressing alphaMbeta2 or the individual constituent chains on their surface, we analyzed the contributions of the alphaM or beta2 subunits to functional responses mediated by the integrin. In cells expressing only alphaM or beta2, the individual subunits were not associated with the endogenous integrins of the cells, and other partners for the subunits were not detected by surface labeling and immunoprecipitation under a variety of conditions. The alphaM cells mediated adhesion and spreading on a series of alphaMbeta2 ligands (fibrinogen, Factor X, iC3b, ICAM-1 (intercellular adhesion molecule-1), and denatured ovalbumin) but could not support cell migration to any of these. The spreading of the alphaM cells suggested an unanticipated linkage of this subunit to the cytoskeleton. The beta2 cells supported migration and attachment but not spreading on a subset of the alphaMbeta2 ligands. The heterodimeric receptor and its individual subunits were purified from the cells by affinity chromatography and recapitulated the ligand binding properties of the corresponding cell lines. These data indicate that each subunit of alphaMbeta2 contributes distinct properties to alphaMbeta2 and that, in most but not all cases, the response of the integrin is a composite of the functions of its individual subunits.
Solovjov
Dmitry A
DA
Joseph J. Jacobs Center for Thrombosis and Vascular Biology, Department of Molecular Cardiology, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
Pluskota
Elzbieta
E
Plow
Edward F
EF
D039481:CD11b Antigen / Q000737:chemistry / Q000378:metabolism*; D018821:CD18 Antigens / Q000737:chemistry / Q000378:metabolism*; D002413:Cations, Divalent / Q000494:pharmacology; D002448:Cell Adhesion; D002460:Cell Line; D002465:Cell Movement; D048430:Cell Shape; D000939:Epitopes; D005434:Flow Cytometry; D006801:Humans; D007962:Leukocytes; D008024:Ligands; D016177:Macrophage-1 Antigen / Q000737:chemistry* / Q000378:metabolism*; D017510:Protein Folding; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism; D013379:Substrate Specificity
D039481:CD11b Antigen; D018821:CD18 Antigens; D002413:Cations, Divalent; D000939:Epitopes; D008024:Ligands; D016177:Macrophage-1 Antigen; D021122:Protein Subunits