Neurexins, neuroligins and LRRTMs: synaptic adhesion getting fishy.
Neurexins, neuroligins and LRRTMs: synaptic adhesion getting fishy.
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DOI：
10.1111/j.1471-4159.2010.07141.x
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发表时间：
2011-06
影响因子：
4.7
通讯作者：
Washbourne P
中科院分区：
文献类型：
--
作者：
Wright GJ;Washbourne P
最近的研究发现，富含亮氨酸的重复蛋白LRRTM2是Neurexins的突触后配体。Neurexins还结合突触后黏附分子，神经连接蛋白。所有这三个基因家族都与神经发育障碍的病因有关，特别是自闭症谱系障碍(ASDS)和精神分裂症。Neurexins的结合混乱现在是否暗示了突触的复杂合作或冗余？虽然最近对神经元原代培养和系统的细胞外蛋白质相互作用筛选的研究表明，这些系统的终结性作用，我们认为，研究这些相互作用在发育中的斑马鱼胚胎或幼虫可能有助于更多地了解它们在体内突触发生过程中的功能。这些基因家族最近在斑马鱼中得到了广泛的表征，显示出与人类基因高度保守的序列。斑马鱼更简单的电路，再加上表达模式的特征，一直到单个可识别的神经元，以及快速敲除或过度表达多个基因的能力，有助于剖析复杂的相互作用途径。此外，进行高通量药物筛选的能力表明，这些小型脊椎动物在确定治疗自闭症的药理方法方面可能非常有用。
Recent studies have identified the leucine rich repeat protein LRRTM2 as a postsynaptic ligand of Neurexins. Neurexins also bind the postsynaptic adhesion molecules, Neuroligins. All three families of genes have been implicated in the etiologies of neurodevelopmental disorders, specifically autism spectrum disorders (ASDs) and schizophrenia. Does the binding promiscuity of Neurexins now suggest complex cooperativity or redundancy at the synapse? While recent studies in primary neuronal cultures and also systematic extracellular protein interaction screens suggest summative effects of these systems, we propose that studying these interactions in the developing zebrafish embryo or larvae may shed more light on their functions during synaptogenesis in vivo. These gene families have recently been extensively characterized in zebrafish, demonstrating high sequence conservation with the human genes. The simpler circuitry of the zebrafish, together with the characterization of the expression patterns down to single, identifiable neurons and the ability to knock-down or overexpress multiple genes in a rapid way lend themselves to dissecting complex interaction pathways. Furthermore, the capability of performing high-throughput drug screens suggests that these small vertebrates may prove extremely useful in identifying pharmacological approaches to treating ASDs.
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影响因子：
14.8
作者：
Biederer, Thomas;Scheiffele, Peter
通讯作者：
Scheiffele, Peter
DOI：
10.1073/pnas.0801383105
发表时间：
2008-04-29
影响因子：
11.1
作者：
Bolliger, Marc F.;Pei, Jimin;Sudhof, Thomas C.
通讯作者：
Sudhof, Thomas C.
影响因子：
7
作者：
Bushell, K. Mark;Sollner, Christian;Wright, Gavin J.
通讯作者：
Wright, Gavin J.
影响因子：
56.9
作者：
Biederer, T;Sara, Y;Südhof, TC
通讯作者：
Südhof, TC
影响因子：
3.5
作者：
Chih, B;Afridi, SK;Scheiffele, P
通讯作者：
Scheiffele, P