Vinet Adrien F, Fiedler Thomas, Studer Vera, Froquet Romain, Dardel Anna, Cosson Pierre, Pieters Jean
Biozentrum, University of Basel, 4056 Basel, Switzerland Faculty of Medicine, University of Geneva, CH-1211 Geneva 4, Switzerland.
Mol Biol Cell. 2014 Mar;25(5):688-701. doi: 10.1091/mbc.E13-04-0219. Epub 2014 Jan 8.
Many biological systems respond to environmental changes by activating intracellular signaling cascades, resulting in an appropriate response. One such system is represented by the social amoeba Dictyostelium discoideum. When food sources become scarce, these unicellular cells can initiate a cAMP-driven multicellular aggregation program to ensure long-term survival. On starvation, the cells secrete conditioned medium factors that initiate cAMP signal transduction by inducing expression of genes such as cAMP receptors and adenylate cyclase. The mechanisms involved in the activation of the first pulses of cAMP release have been unclear. We here show a crucial role for the evolutionarily conserved protein coronin A in the initiation of the cAMP response. On starvation, coronin A-deficient cells failed to up-regulate the expression of cAMP-regulated genes, thereby failing to initiate development, despite a normal prestarvation response. Of importance, external addition of cAMP to coronin A-deficient cells resulted in normal chemotaxis and aggregate formation, thereby restoring the developmental program and suggesting a functional cAMP relay in the absence of coronin A. These results suggest that coronin A is dispensable for cAMP sensing, chemotaxis, and development per se but is part of a signal transduction cascade essential for system initiation leading to multicellular development in Dictyostelium.
许多生物系统通过激活细胞内信号级联反应来响应环境变化，从而产生适当的反应。社会变形虫盘基网柄菌（Dictyostelium discoideum）所代表的就是这样一种系统。当食物来源变得稀缺时，这些单细胞会启动一个由环磷酸腺苷（cAMP）驱动的多细胞聚集程序，以确保长期生存。在饥饿状态下，细胞会分泌条件培养基因子，通过诱导环磷酸腺苷受体和腺苷酸环化酶等基因的表达来启动环磷酸腺苷信号转导。环磷酸腺苷释放的第一个脉冲激活所涉及的机制尚不清楚。我们在此表明，进化上保守的蛋白冠蛋白A在环磷酸腺苷反应的启动中起关键作用。在饥饿状态下，缺乏冠蛋白A的细胞无法上调环磷酸腺苷调节基因的表达，因此尽管饥饿前反应正常，但仍无法启动发育。重要的是，向缺乏冠蛋白A的细胞外添加环磷酸腺苷会导致正常的趋化性和聚集体形成，从而恢复发育程序，并表明在没有冠蛋白A的情况下存在功能性的环磷酸腺苷信号传递。这些结果表明，冠蛋白A对于环磷酸腺苷感知、趋化性和发育本身并非必需，但它是盘基网柄菌中导致多细胞发育的系统启动所必需的信号转导级联反应的一部分。
