A novel cGMP signalling pathway mediating myosin phosphorylation and chemotaxis in Dictyostelium

A novel cGMP signalling pathway mediating myosin phosphorylation and chemotaxis in Dictyostelium
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DOI：
10.1093/emboj/cdf438
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发表时间：
2002-09-02
期刊：
EMBO JOURNAL
影响因子：
11.4
通讯作者：
Van Haastert, PJM
Van Haastert, PJM
中科院分区：
生物学1区
文献类型：
--
作者：
Bosgraaf, L;Russcher, H;Van Haastert, PJM

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盘基网柄菌细胞的趋化刺激导致 cGMP 水平短暂增加，以及肌球蛋白 II 重链和调节轻链的短暂磷酸化。在盘基网柄菌属中，两种鸟苷酸环化酶和四种候选 cGMP 结合蛋白 (GbpA-GbpD) 与 cGMP 信号传导有关。 GbpA 和 GbpB 是具有 Zn2+-水解酶结构域的同源蛋白。 gbpA/gbpB 基因双破坏导致 cGMP 磷酸二酯酶活性降低，基础 cGMP 水平和刺激 cGMP 水平增加 10 倍。与野生型细胞相比，gbpA(-)B(-) 细胞的趋化性与肌球蛋白 II 磷酸化增加有关；外侧伪足的形成受到抑制，导致趋化性增强。 GbpC 与 GbpD 同源，包含 Ras、MAPKKK 和 Ras-GEF 结构域。 gbp 基因的失活表明只有 GbpC 具有高亲和力 cGMP 结合活性。在缺乏 GbpC 和 GbpD 的突变体或缺乏鸟苷酸环化酶的突变体中，肌球蛋白磷酸化、细胞骨架中肌球蛋白的组装以及趋化性均严重受损。因此，一种新型的 cGMP 信号级联对于盘基网柄菌的趋化作用至关重要，并在此过程中的肌球蛋白 II 调节中发挥着重要作用。
Chemotactic stimulation of Dictyostelium cells results in a transient increase in cGMP levels, and transient phosphorylation of myosin II heavy and regulatory light chains. In Dictyostelium, two guanylyl cyclases and four candidate cGMP-binding proteins (GbpA- GbpD) are implicated in cGMP signalling. GbpA and GbpB are homologous proteins with a Zn2+-hydrolase domain. A double gbpA/gbpB gene disruption leads to a reduction of cGMP-phosphodiesterase activity and a 10-fold increase of basal and stimulated cGMP levels. Chemotaxis in gbpA(-)B(-) cells is associated with increased myosin II phosphorylation compared with wild-type cells; formation of lateral pseudopodia is suppressed resulting in enhanced chemotaxis. GbpC is homologous to GbpD, and contains Ras, MAPKKK and Ras-GEF domains. Inactivation of the gbp genes indicates that only GbpC harbours high affinity cGMP-binding activity. Myosin phosphorylation, assembly of myosin in the cytoskeleton as well as chemotaxis are severely impaired in mutants lacking GbpC and GbpD, or mutants lacking both guanylyl cyclases. Thus, a novel cGMP signalling cascade is critical for chemotaxis in Dictyostelium, and plays a major role in myosin II regulation during this process.