STOP and MBP are effectors of microtubule cold stability in oligodendrocytes

MAURICIO R. GALIANO; ANNIE ANDRIEUX; DELOULME J.C.; CHRISTOPHE BOSC; JOB D.; MARTA E. HALLAK

Washington

Congreso; 35th Annual Meeting Society for Neuroscience; 2005

Society for Neuroscience

MBP is a major oligodendrocyte-specific protein essential for oligodendrocyte morphology and subsequent axonal myelination. The molecular mechanisms by which MBP affects cell morphology are still a matter of debate. MBP has been shown to function as a Ca2+/calmodulin regulated microtubule-stabilizing protein in vitro, raising the possibility of a direct connection between MBP and the cytoskeleton. However, the cellular relevance of these observations in oligodendrocytes has been difficult to establish because of a possible overlap between MBP and STOP functions in microtubule stabilization. Here, we have used recently developed mouse models and RNA interference to directly assay the microtubule cold stabilizing activities of MBP and STOP in developing oligodendrocytes. In wild type oligodendrocytes, which contain STOP proteins from earliest stages of differentiation, microtubules are cold-stable throughout maturation. In oligodendrocytes derived from STOP deficient mice, microtubules remain cold labile up to late stages of maturation when MBP is expressed. In intact oligodendrocytes derived from shiverer mice, which are deficient for MBP, microtubules are cold-stable throughout differentiation. STOP suppression in shiverer oligodendrocytes or MBP suppression in STOP deficient oligodendrocytes lead to complete suppression of microtubule cold stability. Thus, the oligodendrocyte STOP variants and MBP induce microtubule cold stability. Based on these results we conclude that MBP is involved in the stability of microtubules and that this could be the basis for MBP requirement for oligodendrocyte structure.