Cohen Laurie D, Ziv Noam E
Technion Faculty of Medicine, Rappaport Institute and Network Biology Research Laboratories, Technion City, Haifa, 32000, Israel.
F1000Res. 2017 May 15;6:675. doi: 10.12688/f1000research.10599.1. eCollection 2017.
Maintaining synaptic integrity and function depends on the continuous removal and degradation of aged or damaged proteins. Synaptic protein degradation has received considerable attention in the context of synaptic plasticity and growing interest in relation to neurodegenerative and other disorders. Conversely, less attention has been given to constitutive, ongoing synaptic protein degradation and the roles canonical degradation pathways play in these processes. Here we briefly review recent progress on this topic and new experimental approaches which have expedited such progress and highlight several emerging principles. These include the realization that synaptic proteins typically have unusually long lifetimes, as might be expected from the remote locations of most synaptic sites; the possibility that degradation pathways can change with time from synthesis, cellular context, and physiological input; and that degradation pathways, other than ubiquitin-proteasomal-mediated degradation, might play key roles in constitutive protein degradation at synaptic sites. Finally, we point to the importance of careful experimental design and sufficiently sensitive techniques for studying synaptic protein degradation, which bring into account their slow turnover rates and complex life cycles.
维持突触完整性和功能依赖于对老化或受损蛋白质的持续清除和降解。在突触可塑性的背景下，突触蛋白降解受到了相当多的关注，并且在神经退行性疾病和其他疾病方面的兴趣也与日俱增。相反，组成性的、持续的突触蛋白降解以及经典降解途径在这些过程中所起的作用却较少受到关注。在此，我们简要回顾了该主题的最新进展以及加速这一进展的新实验方法，并强调了几个新出现的原则。这些原则包括认识到突触蛋白通常具有异常长的寿命，这正如大多数突触位点的偏远位置所预期的那样；降解途径可能会随着合成时间、细胞环境和生理输入而发生变化；以及除泛素 - 蛋白酶体介导的降解外，其他降解途径可能在突触位点的组成性蛋白质降解中起关键作用。最后，我们指出了精心设计实验和采用足够灵敏技术来研究突触蛋白降解的重要性，因为这些技术要考虑到它们缓慢的周转速率和复杂的生命周期。
