Louis J M, Saxe C L, Kimmel A R
Laboratory of Cellular and Developmental Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892.
Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):5969-73. doi: 10.1073/pnas.90.13.5969.
Dictyostelium discoideum is among the best characterized organisms for the study of receptor/guanine nucleotide binding protein-mediated control of differentiation. Dictyostelium grow unicellularly but form fully differentiated multicellular organisms through a developmental program regulated by secreted cAMP activating specific cell-surface receptors. Dictyostelium respond differentially to cAMP at different developmental stages. During early development, expression of certain genes is induced by low-level oscillations of extracellular cAMP. Later, continuous, high cAMP concentrations will promote expression of specific genes in multicellular structures. Here, we show that the cAMP receptor gene CAR1, which is essential for development, utilizes two promoters that are activated at distinct stages of development and respond to different extracellular cAMP conditions. One promoter is active with low-level oscillations of cAMP; exposure to high cAMP concentrations will repress this promoter and induce a second promoter. The CAR1 mRNAs are alternatively spliced but encode identical proteins. Thus, through differential sensitivity to its own ligand, cAMP, two promoters and alternative splicing regulate CAR1 expression during Dictyostelium development.
盘基网柄菌是研究受体/鸟嘌呤核苷酸结合蛋白介导的分化调控的特征最明确的生物体之一。盘基网柄菌以单细胞形式生长，但通过由分泌的cAMP激活特定细胞表面受体来调控的发育程序形成完全分化的多细胞生物体。盘基网柄菌在不同发育阶段对cAMP有不同反应。在发育早期，细胞外cAMP的低水平振荡诱导某些基因的表达。后来，持续的高cAMP浓度会促进多细胞结构中特定基因的表达。在这里，我们表明对发育至关重要的cAMP受体基因CAR1利用两个启动子，它们在不同的发育阶段被激活，并对不同的细胞外cAMP条件作出反应。一个启动子在cAMP低水平振荡时活跃；暴露于高cAMP浓度会抑制该启动子并诱导第二个启动子。CAR1 mRNA经过可变剪接，但编码相同的蛋白质。因此，通过对自身配体cAMP的不同敏感性，两个启动子和可变剪接在盘基网柄菌发育过程中调节CAR1的表达。
