Synuclein Regulates Synaptic Vesicle Clustering and Docking at a Vertebrate Synapse.
Synuclein Regulates Synaptic Vesicle Clustering and Docking at a Vertebrate Synapse.
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DOI：
10.3389/fcell.2021.774650
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发表时间：
2021
影响因子：
5.5
通讯作者：
Morgan JR
中科院分区：
文献类型：
--
作者：
Fouke KE;Wegman ME;Weber SA;Brady EB;Román-Vendrell C;Morgan JR
神经传递主要依赖于活动区小突触囊泡（SV）中神经递质的胞吐释放。因此，神经元必须维持足够的SV池聚集在突触处，以维持有效的神经传递。已经确定磷蛋白突触蛋白1调节SV在突触处的聚集。在这里，我们证明，突触核蛋白，另一个SV相关蛋白和突触蛋白结合伙伴，也调制SV群集在脊椎动物突触。当急性引入未受刺激的七鳃鳗网状脊髓突触时，针对α-突触核蛋白的N-末端结构域的泛突触核蛋白抗体诱导突触处SV的显著损失。对接的SV和SV的远端储备池都被耗尽，导致突触处的总膜损失。相反，针对其他两种丰富的SV相关蛋白，突触囊泡糖蛋白2（SV 2）和囊泡相关膜蛋白（VAMP/synaptobrevin）的抗体，对SV簇的大小或分布没有影响。突触核蛋白扰动引起突触处SV数量的剂量依赖性减少。有趣的是，大SV集群似乎分散成较小的SV集群，以及个别SV。因此，突触核蛋白调节SV在静息突触处的聚集，以及SV在活动区的对接。这些发现揭示了突触核蛋白在突触中的新作用，并为与α-突触核蛋白功能障碍相关的疾病（如帕金森病）提供了重要见解。
Neurotransmission relies critically on the exocytotic release of neurotransmitters from small synaptic vesicles (SVs) at the active zone. Therefore, it is essential for neurons to maintain an adequate pool of SVs clustered at synapses in order to sustain efficient neurotransmission. It is well established that the phosphoprotein synapsin 1 regulates SV clustering at synapses. Here, we demonstrate that synuclein, another SV-associated protein and synapsin binding partner, also modulates SV clustering at a vertebrate synapse. When acutely introduced to unstimulated lamprey reticulospinal synapses, a pan-synuclein antibody raised against the N-terminal domain of α-synuclein induced a significant loss of SVs at the synapse. Both docked SVs and the distal reserve pool of SVs were depleted, resulting in a loss of total membrane at synapses. In contrast, antibodies against two other abundant SV-associated proteins, synaptic vesicle glycoprotein 2 (SV2) and vesicle-associated membrane protein (VAMP/synaptobrevin), had no effect on the size or distribution of SV clusters. Synuclein perturbation caused a dose-dependent reduction in the number of SVs at synapses. Interestingly, the large SV clusters appeared to disperse into smaller SV clusters, as well as individual SVs. Thus, synuclein regulates clustering of SVs at resting synapses, as well as docking of SVs at the active zone. These findings reveal new roles for synuclein at the synapse and provide critical insights into diseases associated with α-synuclein dysfunction, such as Parkinson’s disease.
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DOI：
10.1523/jneurosci.0924-08.2008
发表时间：
2008-10-22
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Gitler D;Cheng Q;Greengard P;Augustine GJ
通讯作者：
Augustine GJ
影响因子：
2.5
作者：
Busch, David J.;Morgan, Jennifer R.
通讯作者：
Morgan, Jennifer R.
DOI：
10.1083/jcb.200212140
发表时间：
2003-05-26
期刊：
The Journal of cell biology
影响因子：
--
作者：
Bloom O;Evergren E;Tomilin N;Kjaerulff O;Löw P;Brodin L;Pieribone VA;Greengard P;Shupliakov O
通讯作者：
Shupliakov O
影响因子：
16.2
作者：
Bendor JT;Logan TP;Edwards RH
通讯作者：
Edwards RH
DOI：
10.1073/pnas.1005005107
发表时间：
2010-11-09
影响因子：
11.1
作者：
Greten-Harrison, Becket;Polydoro, Manuela;Chandra, Sreeganga S.
通讯作者：
Chandra, Sreeganga S.