Kimmel A R
Dev Biol. 1987 Jul;122(1):163-71. doi: 10.1016/0012-1606(87)90342-3.
Alterations in cAMP concentrations have been implicated in developmentally regulated gene expression in Dictyostelium. Using a variety of culture conditions to control the metabolism of cAMP during cytodifferentiation, I have examined the role of the cyclic nucleotide in development. Conditions which allow intracellular synthesis of cAMP promote the normal developmental repression of gene M4-1 by a mechanism which is completely independent of the formation of multicellular aggregates. If, however, cells are inhibited in their ability to activate adenylate cyclase and, thus, intracellular cAMP signaling, they prove unable to repress M4-1, even in the presence of exogenous cAMP. In contrast, expression of genes which exhibit maximal activity after aggregate formation depends upon accumulation of extracellular cAMP. Inhibition of intracellular cAMP signaling does not prevent the expression of these genes if cultures are simultaneously exposed to high levels of exogenously added extracellular cAMP. These results indicate that there are at least two independent mechanisms involved in the developmental regulation of gene expression by cAMP in Dictyostelium. I discuss plausible molecular mechanisms through which cAMP might alter gene expression.
环磷酸腺苷（cAMP）浓度的变化与盘基网柄菌发育调控的基因表达有关。利用多种培养条件来控制细胞分化过程中cAMP的代谢，我研究了环核苷酸在发育中的作用。允许细胞内合成cAMP的条件通过一种完全独立于多细胞聚集体形成的机制促进基因M4 - 1的正常发育抑制。然而，如果细胞激活腺苷酸环化酶的能力受到抑制，从而细胞内cAMP信号传导受到抑制，那么即使存在外源性cAMP，它们也无法抑制M4 - 1。相反，在聚集体形成后表现出最大活性的基因的表达取决于细胞外cAMP的积累。如果培养物同时暴露于高水平的外源性添加的细胞外cAMP，抑制细胞内cAMP信号传导并不会阻止这些基因的表达。这些结果表明，在盘基网柄菌中，至少有两种独立的机制参与cAMP对基因表达的发育调控。我讨论了cAMP可能改变基因表达的合理分子机制。
