Todd Richard B, Fraser James A, Wong Koon Ho, Davis Meryl A, Hynes Michael J
Department of Genetics, The University of Melbourne, Victoria 3010, Australia.
Eukaryot Cell. 2005 Oct;4(10):1646-53. doi: 10.1128/EC.4.10.1646-1653.2005.
Both the availability and the quality of nutrients affect cellular functions by controlling gene activity. AreA, a member of the GATA family of transcription factors, globally activates expression of genes involved in nitrogen source utilization in Aspergillus nidulans. The quality of the nitrogen source determines the level and activation capacity of AreA through controls at the level of areA mRNA stability and by interaction of AreA with the corepressor NmrA. The availability of potential nitrogen sources also affects the activation capacity of AreA. We show that the complete absence of a nitrogen source results in an enhanced level of AreA-dependent gene expression and that this response is independent of mechanisms regulating AreA activity in response to nitrogen source quality. During nitrogen starvation AreA accumulates in the nucleus, but the presence of a potential nitrogen source or carbon starvation prevents this accumulation. Furthermore, accumulated AreA is rapidly lost from the nuclei of nitrogen-starved cells when a nitrogen source is supplied or when a carbon source is absent, and this accompanies arrest of the AreA-dependent nitrogen starvation response on regulated gene expression. By the generation of a leptomycin B-sensitive mutant, we have been able to show that nuclear exit occurs via the CrmA exportin. We conclude that sensing mechanisms discriminate between starvation and the presence of potential nutrients that can signal to the AreA transcription factor. Nitrogen source availability, but not quality, affects nuclear accumulation by regulating nuclear exit of AreA, providing a rapid response to changes in the supply of nutrients.
营养物质的可利用性和质量均通过控制基因活性来影响细胞功能。AreA是转录因子GATA家族的成员之一,可全局激活构巢曲霉中参与氮源利用的基因表达。氮源的质量通过控制areA mRNA稳定性以及AreA与共抑制因子NmrA的相互作用来决定AreA的水平和激活能力。潜在氮源的可利用性也会影响AreA的激活能力。我们发现完全缺乏氮源会导致AreA依赖的基因表达水平增强,并且这种反应独立于响应氮源质量调节AreA活性的机制。在氮饥饿期间,AreA在细胞核中积累,但潜在氮源的存在或碳饥饿会阻止这种积累。此外,当提供氮源或缺乏碳源时,积累的AreA会迅速从氮饥饿细胞的细胞核中消失,这伴随着对调控基因表达的AreA依赖的氮饥饿反应的停止。通过产生对雷帕霉素B敏感的突变体,我们已经能够证明核输出是通过CrmA输出蛋白发生的。我们得出结论,传感机制能够区分饥饿和潜在营养物质的存在,而潜在营养物质可以向AreA转录因子发出信号。氮源的可利用性而非质量通过调节AreA的核输出影响核积累,从而对营养物质供应的变化提供快速反应。