Neurobeachin is required postsynaptically for electrical and chemical synapse formation.
Neurobeachin is required postsynaptically for electrical and chemical synapse formation.
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DOI：
10.1016/j.cub.2014.10.071
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发表时间：
2015-01-05
期刊：
影响因子：
9.2
通讯作者：
Moens, Cecilia B.
中科院分区：
文献类型：
--
作者：
Miller, Adam C.;Voelker, Lisa H.;Shah, Arish N.;Moens, Cecilia B.
神经网络及其功能由突触定义，突触是一种专门用于细胞间通信的粘连，可以是化学的，也可以是电的。在化学突触，神经元之间的传递是由神经递质介导的，而在电突触，直接的离子和代谢耦合通过神经元之间的缝隙连接发生。电突触发生所需的分子途径尚不清楚，它们是否与化学突触具有相同的形成机制也不清楚。在这里，使用斑马鱼的正向遗传筛查，我们发现自闭症相关基因Neurobeachin(Nbea)编码一种含有海滩结构域的蛋白，涉及膜内运输，对于电和化学突触的形成都是必需的。此外，我们发现NBEA对于轴突的形成和早期树突的生长是必不可少的，但对于维持树突的复杂性是必需的。这些突触和形态缺陷与行为表现的缺陷有关。使用可单独识别的神经元为突变型或野生型的嵌合动物，我们发现NbeA在突触后神经元中自主地是突触形成和树突树枝形成的必要条件和充分条件。我们的数据发现了电和化学突触形成之间令人惊讶的联系，并表明NBEA在突触后神经元中扮演着协调树突形态与突触发生的关键调节因子。
Neural networks and their function are defined by synapses, which are adhesions specialized for intercellular communication that can be either chemical or electrical. At chemical synapses transmission between neurons is mediated by neurotransmitters, while at electrical synapses direct ionic and metabolic coupling occurs via gap junctions between neurons. The molecular pathways required for electrical synaptogenesis are not well understood and whether they share mechanisms of formation with chemical synapses is not clear. Here, using a forward genetic screen in zebrafish we find that the autism-associated gene neurobeachin (nbea), which encodes a BEACH-domain containing protein implicated in endomembrane trafficking, is required for both electrical and chemical synapse formation. Additionally, we find that nbea is dispensable for axonal formation and early dendritic outgrowth, but is required to maintain dendritic complexity. These synaptic and morphological defects correlate with deficiencies in behavioral performance. Using chimeric animals in which individually identifiable neurons are either mutant or wildtype we find that Nbea is necessary and sufficient autonomously in the postsynaptic neuron for both synapse formation and dendritic arborization. Our data identify a surprising link between electrical and chemical synapse formation and show that Nbea acts as a critical regulator in the postsynaptic neuron for the coordination of dendritic morphology with synaptogenesis.
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影响因子：
16.2
作者：
OMalley, DM;Kao, YH;Fetcho, JR
通讯作者：
Fetcho, JR
影响因子：
5.8
作者：
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DOI：
10.1073/pnas.0804793105
发表时间：
2008-08-26
影响因子：
11.1
作者：
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通讯作者：
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影响因子：
34.7
作者：
Pereda, Alberto E.
通讯作者：
Pereda, Alberto E.
DOI：
10.1016/j.bbrc.2011.07.110
发表时间：
2011-09-02
影响因子：
3.1
作者：
del Pino, Isabel;Paarmann, Ingo;Betz, Heinrich
通讯作者：
Betz, Heinrich