Novel role for the Lu/BCAM-spectrin interaction in actin cytoskeleton reorganization

Emmanuel Collec , Marie-Christine Lecomte , Wassim El-Nemer , Yves Colin , Caroline Le van Kim (1)

1 DSIMB Réunion - Dynamique des Structures et Interactions des Macromolécules Biologiques - Pôle de La Réunion

Lu/BCAM is a laminin 511/521 receptor, expressed in erythroid and endothelial cells, and in epithelial tissues. The RK573-574 motif of Lu/BCAM cytoplasmic domain interacts with aI-spectrin, the main component of the membrane skeleton in red blood cells. We report that Lu/BCAM binds to the non-erythroid aII-spectrin via the RK573-574 motif. Alanine substitution of this motif abolished the Lu/BCAM-spectrin interaction, enhanced Lu/BCAM half-life at the MDCK cell surface and increased Lu/BCAM-mediated cell adhesion and spreading on laminin 511/521. We showed that the Lu/BCAM-spectrin interaction mediated actin reorganization during cell adhesion and spreading on laminin 511/521. This interaction was involved in a laminin 511/521 to actin signaling pathway leading to stress fibers formation. This skeleton rearrangement was associated with an activation of the small GTP binding protein RhoA, which depended on the integrity of the Lu/BCAM laminin 511/521 binding site. It also required the Lu/BCAM-aII-spectrin interaction since its disruption decreased stress fibers formation and RhoA activation. We conclude that the Lu/BCAM-spectrin interaction is required for stress fibers formation during cell spreading on laminin 511/521 and that spectrin acts as a signal relay between laminin 511/521 and actin that is involved in actin dynamics.

Mots clés: Life Sciences

Emmanuel Collec, Marie-Christine Lecomte, Wassim El-Nemer, Yves Colin, Caroline Le van Kim. Novel role for the Lu/BCAM-spectrin interaction in actin cytoskeleton reorganization. Biochemical Journal, 2011, 436 (3), pp.699-708. ⟨10.1042/BJ20101717⟩. ⟨hal-00596275⟩