WldS protection distinguishes axon degeneration following injury from naturally occurring developmental pruning
WldS protection distinguishes axon degeneration following injury from naturally occurring developmental pruning
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DOI：
10.1016/j.neuron.2006.05.013
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发表时间：
2006-06-15
期刊：
影响因子：
16.2
通讯作者：
Luo, Liqun
中科院分区：
文献类型：
--
作者：
Hoopfer, Eric D.;McLaughlin, Todd;Luo, Liqun
从昆虫到哺乳动物的神经系统中，轴突退化导致的轴突修剪重塑了旺盛的轴突连接，这是发育适当的神经回路所广泛需要的。发育性轴突变性在形态上类似于损伤性沃勒氏变性，提示类似的潜在机制。正如先前在小鼠中报道的那样，我们发现Wld(s)蛋白在很大程度上延缓了沃勒氏变性。令人惊讶的是，Wld(s)对果蝇或小鼠自然发生的发育性轴突变性没有影响，尽管它可以防止相同发育年龄的同一轴突的损伤性变性。相比之下，泛素-蛋白酶体系统在发育和损伤诱导的轴突变性中都是必需的。我们还发现，在发育性轴突变性过程中，神经胶质细胞表面受体Draper是有效清除轴突碎片所必需的，这与它在损伤性变性中的功能相似。因此，从机制上讲，自然发生的发育性轴突退化和损伤诱导的轴突退化在早期阶段有显著差异，但可能趋同于一个共同的执行途径。
Axon pruning by degeneration remodels exuberant axonal connections and is widely required for the development of proper circuitry in the nervous system from insects to mammals. Developmental axon degeneration morphologically resembles injury-induced Wallerian degeneration, suggesting similar underlying mechanisms. As previously reported for mice, we show that Wld(s) protein substantially delays Wallerian degeneration in files. Surprisingly, Wld(s) has no effect on naturally occurring developmental axon degeneration in flies or mice, although it protects against injury-induced degeneration of the same axons at the same developmental age. By contrast, the ubiquitin-proteasome system is intrinsically required for both developmental and injury-induced axon degeneration. We also show that the glial cell surface receptor Draper is required for efficient clearance of axon fragments during developmental axon degeneration, similar to its function in injury-induced degeneration. Thus, mechanistically, naturally occurring developmental axon pruning by degeneration and injury-induced axon degeneration differ significantly in early steps, but may converge onto a common execution pathway.