Unusually rapid evolution of Neuroligin-4 in mice
Unusually rapid evolution of Neuroligin-4 in mice
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DOI：
10.1073/pnas.0801383105
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发表时间：
2008-04-29
影响因子：
11.1
通讯作者：
Sudhof, Thomas C.
中科院分区：
文献类型：
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作者：
Bolliger, Marc F.;Pei, Jimin;Sudhof, Thomas C.
神经连接蛋白(NLS)是一种突触后细胞黏附分子，由于编码NL3和NL4的基因在罕见的家族性自闭症病例中发生突变，因此与人类的自闭症谱系障碍有关。NLS在进化上是高度保守的，除了在目前可用的小鼠基因组序列组合中没有检测到NL4之外。我们现在证明，小鼠表达一种从其他哺乳动物NL4基因快速进化而来的远距离NL4变体，并且即使在不同的小鼠品系之间也表现出序列差异。尽管存在分歧，小鼠NL4仍与Neurexins结合并被运输到树突棘中，这表明NLS的核心属性在这种分歧的NIL亚型中保留了下来。NL4在小鼠身上选择性的快速进化表明，它在大脑中的功能受到比其他NLS更宽松的控制，这揭示了为什么自闭症谱系障碍患者的NL4突变不是致命的，而是导致一种离散的发育性大脑疾病。
Neuroligins (NLs) are postsynaptic cell-adhesion molecules that are implicated in humans in autism spectrum disorders because the genes encoding NL3 and NL4 are mutated in rare cases of familial autism. NLs are highly conserved evolutionarily, except that no NL4 was detected in the currently available mouse genome sequence assemblies. We now demonstrate that mice express a distant NL4 variant that rapidly evolved from other mammalian NL4 genes and that exhibits sequence variations even between different mouse strains. Despite its divergence, mouse NL4 binds neurexins and is transported into dendritic spines, suggesting that the core properties of NLs are retained in this divergent NIL isoform. The selectively rapid evolution of NL4 in mice suggests that its function in the brain is under less stringent control than that of other NLs, shedding light on why its mutation in autism spectrum disorder patients is not lethal, but instead leads to a discrete developmental brain disorder.