Liu G, Newell P C
Department of Biochemistry, University of Oxford, UK.
Symp Soc Exp Biol. 1993;47:283-95.
Evidence is presented for cyclic GMP having a role as a secondary messenger connecting the cell surface cyclic AMP receptors and cytoskeletal myosin II involved in chemotaxis of amoebae of Dictyostelium. Studies were conducted using mutants whose primary defect is in the structural gene for the cyclic GMP-specific phosphodiesterase (streamer F mutants). These mutants show abnormally prolonged accumulation of cyclic GMP in response to stimulation with the chemoattractant cyclic AMP. Investigation of signal transduction in these mutants indicated that, while events associated with production and relay of cyclic AMP signals were normal, certain events associated with movement were (like the cyclic GMP response) abnormally prolonged and these included myosin II association with the cytoskeleton and inhibition of myosin heavy and light chain phosphorylation. These events can be correlated with the amoebae becoming elongated and transiently decreasing their locomotive speed after chemotactic stimulation. Other mutants studied in which the accumulation of cyclic GMP was reduced or absent produced correspondingly reduced or absent myosin responses. We propose a model in which cyclic GMP (transiently accumulated intracellularly in response to stimulation with extracellular cyclic AMP) induces accumulation of myosin II on the cytoskeleton by inhibiting phosphorylation of the myosin heavy chain. As a consequence, bending of the myosin tail and its dissociation from the cytoskeleton are inhibited.
有证据表明，环鸟苷酸（cGMP）作为第二信使，在连接细胞表面环磷酸腺苷（cAMP）受体与参与盘基网柄菌变形虫趋化作用的细胞骨架肌球蛋白II方面发挥作用。研究使用了主要缺陷在于环鸟苷酸特异性磷酸二酯酶结构基因的突变体（拖尾F突变体）。这些突变体在受到趋化剂环磷酸腺苷刺激时，显示出环鸟苷酸异常长时间的积累。对这些突变体中信号转导的研究表明，虽然与环磷酸腺苷信号产生和传递相关的事件正常，但与运动相关的某些事件（如环鸟苷酸反应）异常延长，这些事件包括肌球蛋白II与细胞骨架的结合以及肌球蛋白重链和轻链磷酸化的抑制。这些事件与趋化刺激后变形虫变长并暂时降低其运动速度有关。研究的其他突变体中，环鸟苷酸的积累减少或不存在，相应地产生了减少或不存在的肌球蛋白反应。我们提出一个模型，其中环鸟苷酸（响应细胞外环磷酸腺苷刺激而在细胞内短暂积累）通过抑制肌球蛋白重链的磷酸化诱导肌球蛋白II在细胞骨架上的积累。因此，肌球蛋白尾部的弯曲及其与细胞骨架的解离受到抑制。
