Diversification of behavior and postsynaptic properties by netrin-G presynaptic adhesion family proteins.
Diversification of behavior and postsynaptic properties by netrin-G presynaptic adhesion family proteins.
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DOI：
10.1186/s13041-016-0187-5
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发表时间：
2016-01-08
期刊：
影响因子：
3.6
通讯作者：
Itohara S
中科院分区：
文献类型：
--
作者：
Zhang Q;Goto H;Akiyoshi-Nishimura S;Prosselkov P;Sano C;Matsukawa H;Yaguchi K;Nakashiba T;Itohara S
脊椎动物特异性神经元基因有望在高级脑功能的多样化和进化中发挥关键作用。其中，糖基磷脂酰肌醇（GPI）锚定的神经元网络蛋白-G亚家族成员在UNC 6/netrin家族是独特的，在许多神经元回路中的差异表达模式，和差异结合能力，其同源同源突触后受体。为了深入了解这些基因在高级大脑功能中的作用，我们使用netrin-G敲除小鼠进行了全面的行为电池。我们发现，最近在进化中出现分歧的两个netrin-G旁系同源物netrin-G1和netrin-G2（基因符号分别为Ntng 1和Ntng 2）负责互补的行为功能。netrin-G2，但不是netrin-G1，编码要求的感觉运动功能。这两个旁系同源基因都负责复杂的脊椎动物特有的认知功能，并对无脊椎动物和脊椎动物之间保守的基本适应性行为进行精细调节，如空间参考和工作记忆，注意力，冲动和焦虑等。值得注意的是，netrin-G1和netrin-G2编码了行为调节的遗传“分工”，选择性地介导不同的任务，甚至同一任务的不同细节。在细胞水平上，netrin-G1和netrin-G2差异调节其同源受体的突触下定位，并在互补的神经通路中区分突触后支架蛋白的性质。突触前netrin-G1和netrin-G2使脊椎动物行为的复杂性多样化，并差异调节突触后特性。我们的研究结果构成了第一个脊椎动物GPI蛋白和突触前粘附分子家族的行为和突触多样化作用的遗传分析。
Vertebrate-specific neuronal genes are expected to play a critical role in the diversification and evolution of higher brain functions. Among them, the glycosylphosphatidylinositol (GPI)-anchored netrin-G subfamily members in the UNC6/netrin family are unique in their differential expression patterns in many neuronal circuits, and differential binding ability to their cognate homologous post-synaptic receptors. To gain insight into the roles of these genes in higher brain functions, we performed comprehensive behavioral batteries using netrin-G knockout mice. We found that two netrin-G paralogs that recently diverged in evolution, netrin-G1 and netrin-G2 (gene symbols: Ntng1 and Ntng2, respectively), were responsible for complementary behavioral functions. Netrin-G2, but not netrin-G1, encoded demanding sensorimotor functions. Both paralogs were responsible for complex vertebrate-specific cognitive functions and fine-scale regulation of basic adaptive behaviors conserved between invertebrates and vertebrates, such as spatial reference and working memory, attention, impulsivity and anxiety etc. Remarkably, netrin-G1 and netrin-G2 encoded a genetic “division of labor” in behavioral regulation, selectively mediating different tasks or even different details of the same task. At the cellular level, netrin-G1 and netrin-G2 differentially regulated the sub-synaptic localization of their cognate receptors and differentiated the properties of postsynaptic scaffold proteins in complementary neural pathways. Pre-synaptic netrin-G1 and netrin-G2 diversify the complexity of vertebrate behaviors and differentially regulate post-synaptic properties. Our findings constitute the first genetic analysis of the behavioral and synaptic diversification roles of a vertebrate GPI protein and presynaptic adhesion molecule family.