EXPRESSION OF RECOMBINANT MYELIN-ASSOCIATED GLYCOPROTEIN IN PRIMARY SCHWANN-CELLS PROMOTES THE INITIAL INVESTMENT OF AXONS BY MYELINATING SCHWANN-CELLS
EXPRESSION OF RECOMBINANT MYELIN-ASSOCIATED GLYCOPROTEIN IN PRIMARY SCHWANN-CELLS PROMOTES THE INITIAL INVESTMENT OF AXONS BY MYELINATING SCHWANN-CELLS
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DOI：
10.1083/jcb.111.3.1171
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发表时间：
1990-09-01
影响因子：
7.8
通讯作者：
SALZER, JL
中科院分区：
文献类型：
--
作者：
OWENS, GC;BOYD, CJ;SALZER, JL
髓鞘相关糖蛋白（Myelin-associated glycoprotein， MAG）是髓鞘胶质细胞表达的一种完整的膜蛋白，具有两种发育调节形式，具有不同的羧基端胞质结构域（L-MAG和S-MAG）。为了研究MAG在髓鞘形成中的作用，利用重组逆转录病毒将MAG cDNA （L-MAG形式）导入体外原代雪旺细胞。获得了稳定感染的细胞群，这些细胞在细胞表面组成性地表达MAG，而不需要正常的神经元接触来诱导表达。L-MAG的组成性表达不影响髓鞘形成。在与纯化的感觉神经元长期共培养中，受感染的雪旺细胞上较高水平的MAG表达降低到形成髓磷脂的细胞上的控制水平。另一方面，与正常雪旺细胞不同，与无髓鞘轴突相关或经历沃勒氏变性的感染雪旺细胞表达高水平的MAG。这表明在髓鞘形成过程中有转录后机制调节MAG的表达。用L-MAG特异性抗体对髓鞘培养物进行免疫染色显示，L-MAG在髓鞘形成的早期阶段通常短暂表达。在与感觉神经元短期共培养中，仅表达L-MAG的受感染雪旺细胞在提供外源基板的情况下，在培养4天后分离并包裹较大的轴突。对照组雪旺细胞很少表现出类似的活性，这与4天后低水平的MAG诱导有关。这些数据有力地表明，L-MAG促进了注定成为髓鞘的轴突的雪旺细胞的初始投资。
Myelin-associated glycoprotein (MAG) is an integral membrane protein expressed by myelinating glial cells that occurs in two developmentally regulated forms with different carboxyterminal cytoplasmic domains (L-MAG and S-MAG). To investigate the role of MAG in myelination a recombinant retrovirus was used to introduce a MAG cDNA (L-MAG form) into primary Schwann cells in vitro. Stably infected populations of cells were obtained that constitutively expressed MAG at the cell surface without the normal requirement for neuronal contact to induce expression. Constitutive expression of L-MAG did not affect myelination. In long term co-culture with purified sensory neurons, the higher level of MAG expression on infected Schwann cells was reduced to control levels on cells that formed myelin. On the other hand, unlike normal Schwann cells, infected Schwann cells associated with nonmyelinated axons or undergoing Wallerian degeneration expressed high levels of MAG. This suggests that a posttranscriptional mechanism modulates MAG expression during myelination. Immunostaining myelinating cultures with an antibody specific to L-MAG showed that L-MAG was normally transiently expressed at the earliest stages of myelination. In short term co-culture with sensory neurons, infected Schwann cells expressing only L-MAG segregated and ensheathed larger axons after 4 d in culture provided that an exogenous basal lamina was supplied. Similar activity was rarely displayed by control Schwann cells correlating with the low level of MAG induction after 4 d. These data strongly suggest that L-MAG promotes the initial investment by Schwann cells of axons destined to be myelinated.