Calcium signalling during chemotaxis.
Calcium signalling during chemotaxis.
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DOI：
10.1002/9780470514696.ch8
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
F. Fay;S. Gilbert;R. Brundage
中科院分区：
文献类型：
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作者：
F. Fay;S. Gilbert;R. Brundage
使用荧光指示剂和数字成像显微镜研究了 Ca2+ 在颗粒蝾螈嗜酸性粒细胞趋化中的作用。为了响应血清化学引诱剂，细胞质 Ca2+ 浓度 ([Ca2+]i) 在极化之前升高。在极化运动细胞中，总是可以看到 [Ca2+]i 梯度（尾部-高-前部-低），并且当细胞转动时，[Ca2+]i 短暂上升，并在细胞运动的新方向上下降最快、最远。这些极化和运动所需的 Ca2+ 信号源自响应肌醇 1,4,5-三磷酸 (InsP3) 释放的内部储存的 Ca2+（因为显微注射的肝素完全阻断它们）。与 InsP3 共同产生的 1,2-二酰基-sn-甘油 (DAG) 对 Ca2+ 信号具有抑制作用，这种作用显然是由蛋白激酶 C 介导的。对笼中 InsP3 的研究表明，InsP3 响应性储存似乎集中在核和微管组织中心区域，并且 InsP3 在细胞内移动如此之快，以至于它实际上是一种全局第二信使。因此，在单向迁移过程中观察到的稳定 [Ca2+] 梯度似乎是由细胞后部 InsP3 响应性 Ca2+ 储备的浓度造成的。相比之下，我们认为运动方向改变之前 [Ca2+] 梯度的重新定向是 InsP3 和 DAG 共同作用的结果，其中 InsP3 作为全局第二信使刺激 Ca2+ 释放，DAG 通过蛋白激酶 C 作为空间限制的第二信使抑制趋化刺激部位附近局部 [Ca2+] 增加。
The role of Ca2+ in chemotaxis of eosinophils from the newt Taricha granulosa was investigated using fluorescent indicators and digital imaging microscopy. In response to serum chemoattractant, cytoplasmic Ca2+ concentration ([Ca2+]i) rises prior to polarization. In polarized locomoting cells [Ca2+]i gradients (tail-high-front-low) are always seen, and when cells turn [Ca2+]i rises transiently and falls fastest and furthest in the new direction of cell motion. These Ca2+ signals, which are required for polarization and locomotion, arise from Ca2+ derived from internal stores released in response to inositol 1,4,5-trisphosphate (InsP3) (because microinjected heparin fully blocks them). 1,2-Diacyl-sn-glycerol (DAG), which is co-produced with InsP3, has an inhibitory effect on Ca2+ signals, an effect apparently mediated by protein kinase C. Studies with caged InsP3 reveal that InsP3-responsive stores appear to be concentrated in the nuclear and microtubule-organizing centre regions and that InsP3 moves so rapidly within the cell that it is effectively a global secondary messenger. Thus, stable [Ca2+] gradients observed during unidirectional migration appear to result from the concentration of InsP3-responsive Ca2+ stores in the rear of the cell. By contrast, we propose that reorientation of the [Ca2+] gradient prior to a change in direction of motion results from the joint actions of InsP3 and DAG, with InsP3 acting as a global secondary messenger stimulating Ca2+ release and DAG, through protein kinase C, acting as a spatially restricted secondary messenger inhibiting [Ca2+] increases locally near the site of chemotactic stimulation.