STOP and MBP are effectors of microtubule cold stability in oligodendrocytes.

MAURICIO R. GALIANO; BOSC C.; ANDRIEUX A.; JOB D.; MARTA E. HALLAK

Iguazú

Congreso; XL Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB); 2004

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB)

We described that oligodendrocytes (Olgs) express a major STOP variant of 89 kDa and two minor variants of 48 and 42 kDa which induce microtubule cold-stability and nocodazole resistance. In these cells, MBP is found associated to the network of microtubules (Mts). MBP has also been shown to function as a calmodulin regulated microtubule stabilizing protein in vitro. Herein, we analyse microtubule stability in Olgs cultures derived from STOP knock out (STOP-/-), MBP deficient (shiverer) and wild type (WT) mice. In WT and shiverer Olgs, which express STOP from early stages of differentiation, Mts are cold stable throughout maturation. In STOP -/- Olgs, Mts are initially cold labile until later stages of maturation when MBP is expressed and localized throughout the cell. To directly assay the microtubule stabilizing activities of MBP and STOPs in Olgs, we performed knock down assays of MBP or STOP expressions by transfection with specific siRNAs. The MBP suppression in STOP -/- Olgs or STOP suppression in shiverer Olgs leads to a complete suppression of microtubule cold-stability. Thus, the oligodendrocyte STOP variants are functional in cells whereas MBP functions as a microtubule stabilizing protein in Olgs. These results suggest that MBP is directly involved in regulation of microtubule stability and may be relevant for oligodendrocyte morphology. Supported by: SeCyT-UNC and CONICET.