Borgen Melissa, Grill Brock
Department of Biomedical Engineering and Science, Florida Institute of Technology, Melbourne, USA.
Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, USA.
J Physiol. 2024 Oct 3. doi: 10.1113/JP286469.
Ubiquitin ligases are important regulators of nervous system development, function and disease. To date, numerous ubiquitin ligases have been discovered that regulate presynaptic biology. Here, we discuss recent findings on presynaptic ubiquitin ligases that include members from the three major ubiquitin ligase classes: RING, RBR and HECT. Several themes emerge based on findings across a range of model systems. A cadre of ubiquitin ligases is required presynaptically to orchestrate development and transmission at synapses. Multiple ubiquitin ligases deploy both enzymatic and non-enzymatic mechanisms, and act as hubs for signalling networks at the synapse. Both excitatory and inhibitory presynaptic terminals are influenced by ligase activity. Finally, there are several neurodevelopmental disorders and neurodegenerative diseases associated with presynaptic ubiquitin ligases. These findings highlight the growing prominence and biomedical relevance of the presynaptic ubiquitin ligase network.
泛素连接酶是神经系统发育、功能及疾病的重要调节因子。迄今为止，已发现众多调节突触前生物学的泛素连接酶。在此，我们讨论关于突触前泛素连接酶的最新研究结果，这些泛素连接酶包括来自三大主要泛素连接酶类别的成员：RING、RBR和HECT。基于一系列模型系统的研究结果，出现了几个共同主题。突触前需要一批泛素连接酶来协调突触的发育和传递。多种泛素连接酶同时运用酶促和非酶促机制，并作为突触处信号网络的枢纽。兴奋性和抑制性突触前终末均受连接酶活性的影响。最后，有几种神经发育障碍和神经退行性疾病与突触前泛素连接酶相关。这些研究结果凸显了突触前泛素连接酶网络日益显著的地位及其与生物医学的相关性。
