MBP as a microtubule stabilizing protein in mature oligodendrocytes

GALIANO M.R, ANDRIEUX A, DELOUME J C, BOSC C, SCHWEITZER A., JOB D. AND HALLAK M.E

JOURNAL OF NEUROSCIENCE RESEARCH

Año: 2006 p. 534 - 541

0360-4012

Abstract Myelin Basic Protein (MBP) is an oligodendrocyte-specific protein essential for oligodendrocyte morphogenesis at late stages of cell differentiation. There is evidence that the morphogenetic function of MBP may be mediated by MBP interaction with the cytoskeleton. Thus, an MBP / cytoplasmic microtubule association has been reported and MBP has Ca2+/calmodulin regulated microtubule cold-stabilizing activity in vitro. However, the unambiguous demonstration of a microtubule stabilizing activity for MBP in cells has been difficult because oligodendrocytes contain variants of STOP (Stable Tubule Only Polypeptide) proteins, which are responsible for microtubule cold-stability in different cell types. Herein, we have used genetic mouse models and RNA interference to assay independently the microtubule cold-stabilizing activities of MBP and of STOP in developing oligodendrocytes. In wild type oligodendrocytes, microtubules were cold-stable throughout maturation consistent with the presence of STOP proteins from early stages of differentiation. In contrast, in oligodendrocytes from STOP deficient mice, microtubules were cold labile in the absence of MBP expression or when MBP expression was restricted to the cell body and became stable in fully differentiated oligodendrocytes where MBP is expressed in cell extensions. The suppression of MBP by RNA interference in STOP deficient oligodendrocytes suppressed microtubule cold stability. Additionally, STOP suppression in oligodendrocytes derived from shiverer mice which lack MBP, lead to the complete suppression of microtubule cold stability at all stages of cell differentiation. These results demonstrate that both STOP and MBP function as microtubule stabilizing proteins in differentiating oligodendrocytes, and could be important for the morphogenetic function of MBP. Keywords: oligodendrocyte; microtubule-stability; cytoskeleton; myelination.2+/calmodulin regulated microtubule cold-stabilizing activity in vitro. However, the unambiguous demonstration of a microtubule stabilizing activity for MBP in cells has been difficult because oligodendrocytes contain variants of STOP (Stable Tubule Only Polypeptide) proteins, which are responsible for microtubule cold-stability in different cell types. Herein, we have used genetic mouse models and RNA interference to assay independently the microtubule cold-stabilizing activities of MBP and of STOP in developing oligodendrocytes. In wild type oligodendrocytes, microtubules were cold-stable throughout maturation consistent with the presence of STOP proteins from early stages of differentiation. In contrast, in oligodendrocytes from STOP deficient mice, microtubules were cold labile in the absence of MBP expression or when MBP expression was restricted to the cell body and became stable in fully differentiated oligodendrocytes where MBP is expressed in cell extensions. The suppression of MBP by RNA interference in STOP deficient oligodendrocytes suppressed microtubule cold stability. Additionally, STOP suppression in oligodendrocytes derived from shiverer mice which lack MBP, lead to the complete suppression of microtubule cold stability at all stages of cell differentiation. These results demonstrate that both STOP and MBP function as microtubule stabilizing proteins in differentiating oligodendrocytes, and could be important for the morphogenetic function of MBP. Keywords: oligodendrocyte; microtubule-stability; cytoskeleton; myelination.in vitro. However, the unambiguous demonstration of a microtubule stabilizing activity for MBP in cells has been difficult because oligodendrocytes contain variants of STOP (Stable Tubule Only Polypeptide) proteins, which are responsible for microtubule cold-stability in different cell types. Herein, we have used genetic mouse models and RNA interference to assay independently the microtubule cold-stabilizing activities of MBP and of STOP in developing oligodendrocytes. In wild type oligodendrocytes, microtubules were cold-stable throughout maturation consistent with the presence of STOP proteins from early stages of differentiation. In contrast, in oligodendrocytes from STOP deficient mice, microtubules were cold labile in the absence of MBP expression or when MBP expression was restricted to the cell body and became stable in fully differentiated oligodendrocytes where MBP is expressed in cell extensions. The suppression of MBP by RNA interference in STOP deficient oligodendrocytes suppressed microtubule cold stability. Additionally, STOP suppression in oligodendrocytes derived from shiverer mice which lack MBP, lead to the complete suppression of microtubule cold stability at all stages of cell differentiation. These results demonstrate that both STOP and MBP function as microtubule stabilizing proteins in differentiating oligodendrocytes, and could be important for the morphogenetic function of MBP. Keywords: oligodendrocyte; microtubule-stability; cytoskeleton; myelination.