Evidences that beta1 integrin and Rac1 are involved in the overriding effect of laminin on myelin-associated glycoprotein inhibitory activity on neuronal cells.
During neurite elongation, migrating growth cones encounter both permissive and inhibitory substrates, such as laminin and MAG (myelin-associated glycoprotein), respectively. Here, we demonstrated on two neuronal cell lines (PC12 and N1E-115), that laminin and collagen hampered, in a dose-dependent manner, MAG inhibitory activity on several integrin functions, i.e., neurite growth, cell adhesion and cell spreading. Using a function blocking antibody, in PC12 cells, we showed that alpha1beta1 integrin is required in these phenomena. In parallel, we observed that MAG perturbs actin dynamics and lamellipodia formation during early steps of cell spreading. This seemed to be independent of RhoA activation, but dependent of Rac-1 inhibition by MAG. Laminin overrode MAG activity on actin and prevented MAG inhibition NGF-induced Rac1 activation. In conclusion, we evidenced antagonistic signaling between MAG receptors and beta1 integrins, in which Rac-1 may have a central function.
Laforest
Sullivan
S
FRE CNRS 2737, Faculté de Pharmacie, 27 Bd Jean Moulin, 13005 Marseille, France.
Milanini
Julie
J
Parat
Fabrice
F
Thimonier
Jean
J
Lehmann
Maxime
M
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002417:Cattle; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D002490:Central Nervous System / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D003094:Collagen / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D025461:Feedback, Physiological / Q000187:drug effects / Q000502:physiology; D020439:Growth Cones / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D039222:Integrin alpha1beta1 / Q000378:metabolism; D019012:Integrin beta1 / Q000378:metabolism*; D007797:Laminin / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D018992:Myelin-Associated Glycoprotein / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D016716:PC12 Cells; D051381:Rats; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*
D000906:Antibodies; D039222:Integrin alpha1beta1; D019012:Integrin beta1; D007797:Laminin; C104739:Mag protein, mouse; D018992:Myelin-Associated Glycoprotein; D011956:Receptors, Cell Surface; D003094:Collagen; D020830:rac1 GTP-Binding Protein