Tyrosine phosphatases Shp1 and Shp2 have unique and opposing roles in oligodendrocyte development.
Tyrosine phosphatases Shp1 and Shp2 have unique and opposing roles in oligodendrocyte development.
复制标题
DOI：
10.1111/j.1471-4159.2010.06596.x
复制
发表时间：
2010-04
影响因子：
4.7
通讯作者：
Colognato H
中科院分区：
文献类型：
--
作者：
Kuo E;Park DK;Tzvetanova ID;Leiton CV;Cho BS;Colognato H
少突胶质细胞祖细胞首先增殖以产生足够的细胞数量，然后分化为产生髓磷脂的少突胶质细胞。然而，这些事件背后的信号转导介质仍然知之甚少。酪氨酸磷酸酶 Shp1 与少突胶质细胞分化有关，因为 Shp1 缺陷的小鼠表现出髓鞘形成不足。 Shp1 同源物 Shp2 最近被证明可以调节星形胶质细胞生成，但其在少突胶质细胞发育中的作用仍不清楚。在此，我们报道少突胶质细胞中的Shp2蛋白水平受到发育调节，少突胶质细胞有丝分裂原促进Shp2磷酸化，但被层粘连蛋白（一种促进少突胶质细胞分化的细胞外基质蛋白）抑制。相比之下，少突胶质细胞祖细胞在Shp2（而非Shp1）耗尽后对有丝分裂原没有反应。与之前的研究一致，Shp1 缺失导致分化少突胶质细胞中髓磷脂碱性蛋白水平降低，并减少髓磷脂膜片的生长。相反，Shp2 缺失并不能阻止少突胶质细胞分化，而是促进髓磷脂膜生长扩大。综上所述，这些数据表明Shp1和Shp2在少突胶质细胞发育中具有不同的功能：Shp2调节少突胶质细胞祖细胞增殖，Shp1调节少突胶质细胞分化。对层粘连蛋白的粘附可能另外提供Shp2活性的外在调节，从而促进从祖细胞向分化少突胶质细胞的转变。
Oligodendrocyte progenitor cells first proliferate to generate sufficient cell numbers and then differentiate into myelin-producing oligodendrocytes. The signal transduction mediators that underlie these events, however, remain poorly understood. The tyrosine phosphatase Shp1 has been linked to oligodendrocyte differentiation as Shp1-deficient mice show hypomyelination. The Shp1 homologue, Shp2, has recently been shown to regulate astrogliogenesis but its role in oligodendrocyte development remains unknown. Here we report that Shp2 protein levels were developmentally regulated in oligodendrocytes, with Shp2 phosphorylation being promoted by oligodendroglial mitogens but suppressed by laminin, an extracellular matrix protein that promotes oligodendroglial differentiation. In contrast, oligodendrocyte progenitors were found to be unresponsive to mitogens following Shp2, but not Shp1, depletion. In agreement with previous studies, Shp1 depletion led to decreased levels of myelin basic protein in differentiating oligodendrocytes, as well as reduced outgrowth of myelin membrane sheets. Shp2 depletion in contrast did not prevent oligodendrocyte differentiation but promoted expanded myelin membrane outgrowth. Taken together these data suggest that Shp1 and Shp2 have distinct functions in oligodendrocyte development: Shp2 regulates oligodendrocyte progenitor proliferation and Shp1 regulates oligodendrocyte differentiation. Adhesion to laminin may additionally provide extrinsic regulation of Shp2 activity and thus promote the transition from progenitor to differentiating oligodendrocyte.
登录
查看更多内容
DOI：
10.1083/jcb.85.3.890
发表时间：
1980-06
期刊：
The Journal of cell biology
影响因子：
--
作者：
McCarthy KD;de Vellis J
通讯作者：
de Vellis J
DOI：
10.1523/jneurosci.0888-09.2009
发表时间：
2009-09-23
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Relucio J;Tzvetanova ID;Ao W;Lindquist S;Colognato H
通讯作者：
Colognato H
影响因子：
16.2
作者：
Gauthier, Andree S.;Furstoss, Olivia;Miller, Freda D.
通讯作者：
Miller, Freda D.
影响因子：
7.8
作者：
Colognato, Holly;Ramachandrappa, Shwetha;Olsen, Inger M;ffrench-Constant, Charles
通讯作者：
ffrench-Constant, Charles
影响因子：
4.8
作者：
Montagner, A;Yart, A;Raynal, P
通讯作者：
Raynal, P