The carboxi-terminal domain of myelin basic protein mediates microtubules stability.

DURAND E.S.; GALIANO M.R.; MIRANDA A.L.; BOSC C.; HALLAK M.E.

Mar del Plata

Congreso; XXX Annual Meeting and SAN-ISN Small Conference and Course; 2015

Sociedad Argentina de Investigación en Neurociencias (SAN)

Myelin Basic Protein (MBP), an essential component of myelin compact membranes, is capable to stabilize microtubules (Mts) in differentiated oligodendrocytes. As such interaction of MBP with Mts is regulated by calmodulin (CaM), further studies were performed at molecular levels. Four different CaM-binding sites were identified on classic MBP isoforms, localized in the spliced exons and the carboxi-terminal (C-terminal) portion. HeLa cells were transfected with different MBP variants to determine the relevance of these CaM-binding sites on the interaction of MBP with Mts. The colocalization of the different isoforms of MBP with CaM is impaired in those variants whose C-terminal portion is deleted. To analyze which MBP variants are capable to stabilize Mts, cells are exposed to cold temperature. We determined that mainly the MBP isoforms 2, 4 and 6 are capable to preserve a cold stable Mts. Such Mts stabilization is lost when isoforms are deleted in the C-terminal portion. As the tubulin-binding sites of MBP were proposed to be comprised within sequence codified by exon III and IV (common to the different MBP isoforms), these results suggest that the CaM-binding site localized at C-terminal portion of these MBP isoforms significantly modulates the microtubule stabilization. Further studies directed to identify the microtubule binding sites of MBP would help to better understand the regulatory activity of the identified CaM-binding domains onto MBP-Mts interactions.Supported by CONICET, FONCyT and SECyT