The regulation of MBP by its interaction with Ca2+-calmodulin is specific for each isoform and CaM binding-site deiminations impair MBP-CaM interaction

DURAND E.S.; GALIANO M.R.; BOSC C.; FRANK R.; HALLAK M.E.

Huerta Grande, Córdoba

Congreso; II Reunión Conjunta de Neurociencias; 2010

Sociedad Argentina de Investigación en Neurociencias (SAN)

MBP is essential for formation of myelin compact membranes in central nervous system. The interactions of MBP with different cell components are regulated by CaM and by various post-translational modifications. In this regard, we studied the MBP-CaM interaction by immobilized peptide array. There are six variants of MBP encoded by a single gene and generated by alternative splicing. We performed the peptide array with the amino acid sequence of the longest variant that contains all exons, MBP isoform 1, and we find that CaM binds to three distinct domains that lay in the exons involved in alternative splicing. These CaM-binding sites differ in the strength of interaction; the strongest is located between exons VI and VII of MBP isoforms 1, 2, 3 and 5. In isoforms 4 and 6 the junction of exon V with exon VII generates a weak CaM-binding site. In addition, each CaM-binding site has three serines and two arginines that can undergo the most common post-translational modifications of MBP such as phosphorylation or deimination respectively. Substitution of arginine by citrulline in the CaM-binding sites impairs MBP-CaM interaction. Deimination of MBP has been correlated with early development, demyelination process and disease severity in MS. Further studies of the regulation of MBP by CaM and post-translational modifications will help to understand its role in signaling for oligodendrocyte differentiation and myelin formation, and its involvement in the pathogenesis of MS. Supported by CONICET, FONCyT and SECyT