Louhivuori Lauri M, Jansson Linda, Turunen Pauli M, Jäntti Maria H, Nordström Tommy, Louhivuori Verna, Åkerman Karl E
Biomedicum Helsinki, Institute of Biomedicine/Physiology, University of Helsinki , Helsinki, Finland .
Stem Cells Dev. 2015 Mar 15;24(6):701-13. doi: 10.1089/scd.2014.0209. Epub 2014 Dec 17.
The guidance of developing neurons to the right position in the central nervous system is of central importance in brain development. Canonical transient receptor potential (TRPC) channels are thought to mediate turning responses of growth cones to guidance cues through fine control of calcium transients. Proliferating and 1- to 5-day-differentiated neural progenitor cells (NPCs) showed expression of Trpc1 and Trpc3 mRNA, while Trpc4-7 was not clearly detected. Time-lapse imaging showed that the motility pattern of neuronal cells was phasic with bursts of rapid movement (>60 μm/h), changes in direction, and intermittent slow phases or stallings (<40 μm/h), which frequently occurred in close contact with radial glial processes. Genetic interference with the TRPC3 and TRPC1 channel enhanced the motility of NPCs (burst frequency/stalling frequency). TRPC3-deficient cells or cells treated with the TRPC3 blocker pyr3 infrequently changed direction and seldom contacted radial glial processes. TRPC channels are also activated by group I metabotropic glutamate receptors (mGluR1 and mGluR5). As shown here, pyr3 blocked the calcium response mediated through mGluR5 in radial glial processes. Furthermore, 2-methyl-6-(phenylethynyl)pyridine, a blocker of mGluR5, affected the motility pattern in a similar way as TRPC3/6 double knockout or pyr3. The results suggest that radial glial cells exert attractant signals to migrating neuronal cells, which alter their motility pattern. Our results suggest that mGluR5 acting through TRPC3 is of central importance in radial glial-mediated neuronal guidance.
在大脑发育过程中，引导发育中的神经元到达中枢神经系统的正确位置至关重要。典型瞬时受体电位（TRPC）通道被认为通过对钙瞬变的精细控制来介导生长锥对引导信号的转向反应。增殖的以及分化1至5天的神经祖细胞（NPC）显示出Trpc1和Trpc3 mRNA的表达，而Trpc4 - 7未被清晰检测到。延时成像显示，神经元细胞的运动模式呈阶段性，包括快速运动爆发（>60μm/h）、方向改变以及间歇性的缓慢阶段或停滞（<40μm/h），这些情况经常发生在与放射状胶质细胞突起紧密接触时。对TRPC3和TRPC1通道的基因干扰增强了NPC的运动性（爆发频率/停滞频率）。缺乏TRPC3的细胞或用TRPC3阻滞剂pyr3处理的细胞很少改变方向，并且很少与放射状胶质细胞突起接触。TRPC通道也可被I组代谢型谷氨酸受体（mGluR1和mGluR5）激活。如此处所示，pyr3阻断了放射状胶质细胞突起中通过mGluR5介导的钙反应。此外，mGluR5的阻滞剂2 - 甲基 - 6 -（苯乙炔基）吡啶对运动模式的影响与TRPC3/6双敲除或pyr3相似。结果表明，放射状胶质细胞向迁移的神经元细胞施加吸引信号，从而改变它们的运动模式。我们的结果表明，通过TRPC3起作用的mGluR5在放射状胶质细胞介导的神经元引导中至关重要。
