Myelin-associated glycoprotein inhibits axonal regeneration from a variety of neurons via interaction with a sialoglycoprotein
Myelin-associated glycoprotein inhibits axonal regeneration from a variety of neurons via interaction with a sialoglycoprotein
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DOI：
10.1006/mcne.1996.0007
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发表时间：
1996-02-01
影响因子：
3.5
通讯作者：
Filbin, MT
中科院分区：
文献类型：
--
作者：
DeBellard, ME;Tang, S;Filbin, MT
髓鞘相关糖蛋白（MAG）是一种有效的抑制剂轴突再生的小脑神经元和成人背根神经节（DRG）神经元。相反，MAG促进新生DRG神经元的轴突生长。在这里，我们表明，开关MAG从促进到抑制DRG神经元的轴突生长急剧发生在出生后第3天。迄今为止，在所有测试的神经元中，仅观察到DRG神经元的出生后响应开关; MAG抑制所有出生后年龄的视网膜、上级颈神经节、脊髓和海马神经元的轴突生长。此外，MAG以硫酸依赖性方式与其促进和抑制生长的神经元结合。现在我们表明这种结合也是胰蛋白酶敏感的。因此，相互作用是通过唾液酸糖蛋白。MAG与此处测试的所有神经元的结合也是硫酸依赖性的。重要的是，MAG对神经突生长的抑制和促进都被减少或完全消除，这可以通过在生长测定之前对神经元进行去唾液酸化或通过在培养物中包括小的含唾液酸的糖来实现。这些结果表明，MAG可能导致整个神经系统观察到的再生缺乏。此外，MAG可能通过神经元唾液酸糖蛋白直接或间接地对促进和抑制神经突生长发挥作用。
Myelin-associated glycoprotein (MAG) is a potent inhibitor of axonal regeneration from both cerebellar neurons and adult dorsal root ganglion (DRG) neurons. In contrast, MAG promotes axonal growth from newborn DRG neurons. Here, we show that the switch in response to MAG from promotion to inhibition of neurite outgrowth by DRG neurons occurs sharply at Postnatal Day 3. To date, of all the neurons tested a postnatal switch in response is only observed for DRG neurons; MAG inhibits axonal growth from retinal, superior cervical ganglion, spinal, and hippocampal neurons of all postnatal ages. Furthermore, MAG binds to neurons from which it promotes and from which it inhibits outgrowth, in a sialic-acid-dependent manner. Now we show this binding is also trypsin-sensitive. Hence, the interaction is via a sialoglycoprotein. Binding of MAG to all the neurons tested here was also sialic-acid-dependent. Importantly, both inhibition and promotion of neurite outgrowth by MAG are reduced, or abolished completely, either by desialyation of the neurons prior to the outgrowth assay or by including small sialic-acid-bearing sugars in the cultures. These results suggest that MAG is likely to contribute to the lack of regeneration observed throughout the nervous system. Also, it is likely that MAG is exerting its effect, either directly or indirectly, on both promotion and inhibition of neurite outgrowth via a neuronal sialoglycoprotein.