Myelin basic protein functions as a microtubule stabilizing protein in differentiated oligodendrocytes
Myelin basic protein functions as a microtubule stabilizing protein in differentiated oligodendrocytes
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DOI：
10.1002/jnr.20960
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发表时间：
2006-08-15
影响因子：
4.2
通讯作者：
Hallak, M. E.
中科院分区：
文献类型：
--
作者：
Galiano, M. R.;Andrieux, A.;Hallak, M. E.
髓鞘碱性蛋白（MBP）是一种少突胶质细胞特异性蛋白质，在细胞分化的晚期对少突胶质细胞形态发生至关重要。有证据表明，MBP的形态发生功能是由MBP与细胞骨架的相互作用介导的。因此，MBP/细胞质微管协会已被报道，和MBP在体外具有Ca 2 +/钙调素调节的微管冷稳定活性。然而，MBP在细胞中的微管稳定活性的明确证明是困难的，因为少突胶质细胞含有STOP（仅稳定微管多肽）蛋白的变体，其负责不同细胞类型中的微管冷稳定性。在此，我们已经使用遗传小鼠模型和RNA干扰独立测定微管冷稳定活动的MBP和STOP在发展中的少突胶质细胞。在野生型少突胶质细胞中，微管在整个成熟过程中是冷稳定的，这与分化早期阶段STOP蛋白的存在一致。相反，在STOP缺陷小鼠的少突胶质细胞中，在没有MBP表达的情况下，或者当MBP表达仅限于细胞体时，微管是冷不稳定的，并且在完全分化的少突胶质细胞中变得稳定，其中MBP在细胞延伸中表达。在STOP缺陷的少突胶质细胞中通过RNA干扰抑制MBP抑制微管冷稳定性。此外，在来自缺乏MBP的颤抖小鼠的少突胶质细胞中的STOP抑制导致在细胞分化的所有阶段微管冷稳定性的完全抑制。这些结果表明，STOP和MBP在分化少突胶质细胞中作为微管稳定蛋白发挥作用，并且可能对MBR的形态发生功能很重要（c）2006 Wiley-Liss，Inc.
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 is 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, which is 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 that lack MBP led 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 MBR (c) 2006 Wiley-Liss, Inc.