Netrin-1 elevates the level and induces cluster formation of its receptor DCC at the surface of cortical axon shafts in an exocytosis-dependent manner
Netrin-1 elevates the level and induces cluster formation of its receptor DCC at the surface of cortical axon shafts in an exocytosis-dependent manner
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DOI：
10.1016/j.neures.2010.02.004
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发表时间：
2010-06-01
影响因子：
2.9
通讯作者：
Nagashima, Masabumi
中科院分区：
文献类型：
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作者：
Matsumoto, Hideko;Nagashima, Masabumi
在发育过程中，可扩散的轴突引导因子netrin-1通过诱导轴突生长、吸引、排斥和/或在各种类型的神经元中分支，在神经系统的正确布线中发挥各种重要作用。据报道，其受体DCC（在结肠直肠癌中缺失）从细胞内池易位到质膜增强了大鼠脊髓连合轴突响应netrin-1的生长（Bouchard et al.，2004年）。为了找出netrin-1是否诱导DCC易位在大脑皮层神经元，我们研究了DCC的水平和分布在仓鼠解离的皮层轴突的表面响应netrin-1的变化。在皮质轴突轴的表面，我们观察到netrin-1诱发的，胞吐依赖的DCC聚类，这是伴随着DCC水平的升高。细胞表面DCC的这些变化发生在轴突干中，但不发生在生长锥中。综上所述，这些结果表明，细胞表面DCC是由netrin-1通过DCC的易位到质膜，通过在大脑皮层神经元胞吐调节。(C)2010年爱思唯尔爱尔兰有限公司和日本神经科学学会。All rights reserved.
During development, a diffusible axon guidance cue, netrin-1, plays a variety of important roles in the correct wiring of the nervous system by inducing axon outgrowth, attraction, repulsion and/or branching in various types of neurons. It has been reported that translocation of its receptor DCC (deleted in colorectal cancer) from an intracellular pool to the plasma membrane enhances outgrowth of rat spinal commissural axons in response to netrin-1 (Bouchard et al., 2004). To find out whether netrin-1 induces DCC translocation in cerebral cortical neurons, we examined changes in the level and distribution of DCC at the surface of hamster dissociated cortical axons in response to netrin-1. At the surface of cortical axon shafts, we observed netrin-1-evoked, exocytosis-dependent DCC clustering, which was accompanied by elevation of the DCC level. These changes in cell surface DCC occurred in axon shafts, but did not occur in growth cones. Taken together, these results indicate that cell surface DCC is modulated by netrin-1 through translocation of DCC to the plasma membrane via exocytosis in cerebral cortical neurons. (C) 2010 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.