Cholesterol alters the interaction of glycosphingolipid GM3 with alpha5beta1 integrin and increases integrin-mediated cell adhesion to fibronectin.
Integrins bind to their ligand in the extracellular matrix (ECM), such as fibronectin (FN), through a specific interaction between the amino acid motifs in the ligand, and binding sites in the extracellular domains of the integrin molecule generated jointly by its alpha and beta subunits. It has been proposed that membrane cholesterol and glycosphingolipids (GSLs) can regulate integrin-ECM interactions and it has been demonstrated that increased membrane cholesterol leads to increased cell adhesion to FN. Here, we have shown that a specific glycosphingolipid GM3 binds directly to alpha5beta1 integrin and an increase in membrane cholesterol results in the redistribution of GM3-associated alpha5beta1 integrin molecules specifically on the surface that is in contact with the substratum. Our results suggest that GM3-associated alpha5beta1 integrins bind less avidly to FN than GM3-free integrins and that cholesterol and GM3 play an interdependent role in the distribution of alpha5beta1integrin molecules in the membrane and regulation of cell adhesion.
Gopalakrishna
Praturi
P
Centre for Cellular and Molecular Biology, Hyderabad 500 007, India.
Rangaraj
Nandini
N
Pande
Gopal
G
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001665:Binding Sites / Q000502:physiology; D002448:Cell Adhesion / Q000502:physiology; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D005347:Fibroblasts; D005353:Fibronectins / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D005679:G(M3) Ganglioside / Q000276:immunology / Q000378:metabolism*; D039081:Integrin alpha5beta1 / Q000276:immunology / Q000378:metabolism*; D008024:Ligands; D008563:Membrane Lipids / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D051381:Rats; D015854:Up-Regulation / Q000502:physiology
D000906:Antibodies; D005353:Fibronectins; D005679:G(M3) Ganglioside; D039081:Integrin alpha5beta1; D008024:Ligands; D008563:Membrane Lipids; D002784:Cholesterol