Williams J G, Harwood A J, Hopper N A, Simon M N, Bouzid S, Veron M
Imperial Cancer Research Fund, Clare Hall Laboratories, South Mimms, U.K.
Philos Trans R Soc Lond B Biol Sci. 1993 Jun 29;340(1293):305-13. doi: 10.1098/rstb.1993.0072.
During formation of the Dictyostelium slug extracellular cAMP signals direct the differentiation of prespore cells and DIF, a chlorinated hexaphenone, induces the differentiation of prestalk cells. At culmination the slug transforms into a fruiting body, composed of a stalk supporting a ball of spores. A dominant inhibitor of cAMP-dependent protein kinase (PKA) expressed under the control of a prestalk-specific promoter blocks the differentiation of prestalk cells into stalk cells. Analysis of a gene specifically expressed in stalk cells suggests that PKA acts to remove a repressor that prevents the premature induction of stalk cell differentiation by DIF during slug migration. PKA is also necessary for the morphogenetic movement of prestalk cells at culmination. Expression of the PKA inhibitor under control of a prespore-specific promoter blocks the accumulation of prespore mRNA sequences and prevents terminal spore cell differentiation. Thus PKA is essential for progression along both pathways of terminal differentiation but with different mechanisms of action. On the stalk cell pathway it acts to regulate the action of DIF while on the spore cell pathway PKA itself seems to act as the inducer of spore cell maturation. Ammonia, the extracellular signal which regulates the entry into culmination, acts by controlling the intracellular concentration of cAMP and thus exerts its effects via PKA. The fact that PKA is necessary for both prespore and spore gene expression leads us to postulate the existence of a signalling mechanism which converts the progressive rise in cAMP concentration during development into discrete, PKA-regulated gene activation events.
在盘基网柄菌蛞蝓体形成过程中,细胞外的环磷酸腺苷(cAMP)信号引导前孢子细胞的分化,而二氯六苯酮(DIF)则诱导前柄细胞的分化。在发育到顶体期时,蛞蝓体转变为子实体,子实体由支撑着一团孢子的柄组成。一种在前柄特异性启动子控制下表达的环磷酸腺苷依赖性蛋白激酶(PKA)的显性抑制剂会阻断前柄细胞向柄细胞的分化。对在柄细胞中特异性表达的一个基因的分析表明,PKA的作用是去除一种阻遏物,该阻遏物可防止在蛞蝓体迁移过程中DIF过早诱导柄细胞分化。PKA对于顶体期前柄细胞的形态发生运动也是必需的。在前孢子特异性启动子控制下表达PKA抑制剂会阻断前孢子mRNA序列的积累,并阻止孢子细胞的终末分化。因此,PKA对于沿着两条终末分化途径的进展都是必不可少的,但作用机制不同。在柄细胞途径中,它起到调节DIF作用的功能,而在孢子细胞途径中,PKA本身似乎充当孢子细胞成熟的诱导剂。氨作为调节进入顶体期的细胞外信号,通过控制细胞内环磷酸腺苷的浓度起作用,从而通过PKA发挥其效应。PKA对于前孢子和孢子基因表达都是必需的这一事实,使我们推测存在一种信号传导机制,该机制将发育过程中环磷酸腺苷浓度的逐渐升高转化为离散的、由PKA调节的基因激活事件。