Nutrient limitation affects presynaptic structures through dissociable Bassoon autophagic degradation and impaired vesicle release
Nutrient limitation affects presynaptic structures through dissociable Bassoon autophagic degradation and impaired vesicle release
复制标题
DOI：
10.1177/0271678x18786356
复制
发表时间：
2018-11-01
影响因子：
6.3
通讯作者：
Boeckers, Tobias M.
中科院分区：
文献类型：
--
作者：
Catanese, Alberto;Garrido, Debora;Boeckers, Tobias M.
神经元的代谢需求和营养/生长因子的可获得性之间的严重不匹配是几种神经系统疾病的特征，如创伤性脑损伤、中风和低血糖。尽管这种错配的影响已经在细胞生物学水平上进行了研究，但对突触结构和功能的影响还不是很清楚。由于突触活动是最需要能量的神经元功能，它与神经元网络功能直接相关，我们探讨了营养限制(NL)是否影响突触前和突触后终末的超微结构、功能和组成。我们发现，在NL上，突触前终末显示出无序的囊泡池和活动区蛋白Bason(但不是Piccolo)的水平降低。此外，NL触发受损的囊泡释放，这可通过重新给药葡萄糖而逆转，但不能通过阻止自噬或蛋白酶体蛋白降解而逆转。这揭示了突触前结构和囊泡释放之间的不可关联的联系，因为恢复囊泡融合并不一定依赖于对巴松管水平的挽救。因此，我们的数据表明，突触前区对NL高度敏感，恢复突触前功能需要重建代谢供应，而不是阻止局部蛋白质降解。
Acute mismatch between metabolic requirements of neurons and nutrients/growth factors availability characterizes several neurological conditions such as traumatic brain injury, stroke and hypoglycemia. Although the effects of this mismatch have been investigated at cell biological level, the effects on synaptic structure and function are less clear. Since synaptic activity is the most energy-demanding neuronal function and it is directly linked to neuronal networks functionality, we have explored whether nutrient limitation (NL) affects the ultrastructure, function and composition of pre and postsynaptic terminals. We show that upon NL, presynaptic terminals show disorganized vesicle pools and reduced levels of the active zone protein Bassoon (but not of Piccolo). Moreover, NL triggers an impaired vesicle release, which is reversed by re-administration of glucose but not by the blockade of autophagic or proteasomal protein degradation. This reveals a dissociable correlation between presynaptic architecture and vesicle release, since restoring vesicle fusion does not necessarily depend from the rescue of Bassoon levels. Thus, our data show that the presynaptic compartment is highly sensitive to NL and the rescue of presynaptic function requires re-establishment of the metabolic supply rather than preventing local protein degradation.