1. Diversification of behavior and postsynaptic properties by netrin-G presynaptic adhesion family proteins
- Author
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Shigeyoshi Itohara, Kunio Yaguchi, Chie Sano, Qi Zhang, Pavel Prosselkov, Sachiko Akiyoshi-Nishimura, Toshiaki Nakashiba, Hiroshi Matsukawa, and Hiromichi Goto
- Subjects
0301 basic medicine ,Scaffold protein ,animal structures ,Subfamily ,Emotions ,Presynaptic Terminals ,GPI-protein ,Nerve Tissue Proteins ,Netrtin-G1 ,Biology ,Presynapse ,Postsynapse ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Memory ,Molecular evolution ,Postsynaptic potential ,Netrin ,Animals ,Cognitive diversification ,Attention ,Molecular Biology ,Mice, Knockout ,Behavior, Animal ,Research ,fungi ,Brain ,Membrane Proteins ,Netrin-G2 ,Mice, Inbred C57BL ,Phenotype ,030104 developmental biology ,nervous system ,Membrane protein ,Synapses ,embryonic structures ,Netrins ,Sensorimotor Cortex ,Nerve Net ,Disks Large Homolog 4 Protein ,Guanylate Kinases ,Neuroscience ,030217 neurology & neurosurgery - Abstract
Background 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. Results 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. Conclusions 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.
- Published
- 2016
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