Integrin alpha chain cytoplasmic tails regulate "antibody-redirected" cell adhesion, independently of ligand binding.
Here we describe a novel "antibody-redirected cell adhesion" (ARCA) assay. This assay measures heterotypic cell-cell adhesion, resulting from antibody bridging between Fc gamma receptors type II (CD32) on leukocytes, and clustered integrins on adherent cell monolayers. This ARCA activity, facilitated by integrins alpha3 beta1 or alpha4 beta1, required an intact cytoskeleton, but did not involve typical integrin ligand binding sites or divalent cations. Furthermore, deletion of the alpha4 cytoplasmic tail almost completely abrogated integrin ARCA activity, suggesting an alteration of integrin recruitment into adhesive sites. If two or more tail residues were present after the conserved GFFKR motif, then ARCA activity was largely restored. Although alpha4 tail deletion caused loss of ARCA activity, it had no effect on the binding of VCAM-1 to intact alpha4-transfected K562 cells. In conclusion, the integrin alpha chain tail can positively regulate integrin-dependent cell adhesion by a receptor recruitment/clustering mechanism independent of conventional integrin ligand-binding considerations.
Weitzman
J B
JB
Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
Pujades
C
C
Hemler
M E
ME
D008841:Actin Cytoskeleton / Q000187:drug effects; D000818:Animals; D015703:Antigens, CD / Q000502:physiology*; D016466:CHO Cells; D002448:Cell Adhesion; D002478:Cells, Cultured; D006224:Cricetinae; D003571:Cytochalasin B / Q000494:pharmacology; D004492:Edetic Acid / Q000494:pharmacology; D006801:Humans; D039421:Integrin alpha2; D039422:Integrin alpha3; D039441:Integrin alpha4; D016023:Integrins / Q000502:physiology*; D008024:Ligands; D011940:Receptor Aggregation; D017452:Receptors, IgG / Q000502:physiology*; D011994:Recombinant Proteins; D017384:Sequence Deletion; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D015703:Antigens, CD; D039421:Integrin alpha2; D039422:Integrin alpha3; D016023:Integrins; D008024:Ligands; D017452:Receptors, IgG; D011994:Recombinant Proteins; D019010:Vascular Cell Adhesion Molecule-1; D039441:Integrin alpha4; D003571:Cytochalasin B; D004492:Edetic Acid