Role of multiple beta1 integrins in cell adhesion to the disintegrin domains of ADAMs 2 and 3.
ADAM disintegrin domains can support integrin-mediated cell adhesion. However, the profile of which integrins are employed for adhesion to a given disintegrin domain remains unclear. For example, we suggested that the disintegrin domains of mouse sperm ADAMs 2 and 3 can interact with the alpha6beta1 integrin on mouse eggs. Others concluded that these disintegrin domains interact instead with the alpha9beta1 integrin. To address these differing results, we first studied adhesion of mouse F9 embryonal carcinoma cells and human G361 melanoma cells to the disintegrin domains of mouse ADAMs 2 and 3. Both cell lines express alpha6beta1 and alpha9beta1 integrins at their surfaces. Antibodies to the alpha6 integrin subunit inhibited adhesion of both cell lines. An antibody that recognizes human alpha9 integrin inhibited adhesion of G361 cells. VLO5, a snake disintegrin that antagonizes alpha4beta1 and alpha9beta1 integrins, potently inhibited adhesion of both cell lines. We next explored expression of the alpha9 integrin subunit in mouse eggs. In contrast to our ability to detect alpha6beta1, we were unable to convincingly detect alpha9beta1 integrin on the surface of mouse eggs. Moreover, treatment of mouse eggs with 250 nm VLO5, which is 250 fold over its approximately IC(50) for inhibition of somatic cell adhesion, had minimal effect on sperm-egg binding or fusion. We did detect alpha9 integrin protein on epithelial cells of the oviduct. Additional studies showed that antibodies to the alpha6 and alpha7 integrins additively inhibited adhesion of mouse trophoblast stem cells and that an antibody to the alpha4 integrin inhibited adhesion of MOLT-3 cells to these disintegrin domains: Our data suggest that multiple integrins (on the same cell) can participate in adhesion to a given ADAM disintegrin domain and that interactions between ADAMs and integrins may be important for sperm transit through the oviduct.
D051722:ADAM Proteins; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism; D019483:Disintegrins / Q000378:metabolism / Q000494:pharmacology; D054278:Embryonal Carcinoma Stem Cells; D005260:Female; D000072196:Fertilins; D006801:Humans; D039001:Integrin alpha Chains / Q000037:antagonists & inhibitors / Q000378:metabolism; D039041:Integrin alpha4beta1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D019012:Integrin beta1 / Q000187:drug effects / Q000378:metabolism*; D007938:Leukemia / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008666:Metalloendopeptidases / Q000378:metabolism*; D051379:Mice; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism*; D010057:Oviducts / Q000187:drug effects / Q000378:metabolism; D010063:Ovum / Q000187:drug effects / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000502:physiology; D012176:Retinoids / Q000378:metabolism*; D012910:Snake Venoms / Q000494:pharmacology; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism; D014407:Tumor Cells, Cultured
C091976:ADAM 3; D000906:Antibodies; D019483:Disintegrins; D039001:Integrin alpha Chains; D039041:Integrin alpha4beta1; D019012:Integrin beta1; D008562:Membrane Glycoproteins; D012176:Retinoids; D012910:Snake Venoms; C084613:integrin alpha9; D051722:ADAM Proteins; D000072196:Fertilins; D008666:Metalloendopeptidases