The RGS protein Crg2 regulates both pheromone and cAMP signalling in Cryptococcus neoformans.
The RGS protein Crg2 regulates both pheromone and cAMP signalling in Cryptococcus neoformans.
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DOI：
10.1111/j.1365-2958.2008.06417.x
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发表时间：
2008-10
影响因子：
3.6
通讯作者：
Heitman J
中科院分区：
文献类型：
--
作者：
Xue C;Hsueh YP;Chen L;Heitman J
G蛋白通过将细胞外信号转导为细胞内信号和控制细胞对环境信号的反应来协调关键的细胞功能。G蛋白通常作为开关，由G蛋白偶联受体（gpcr）激活，并由G蛋白信号调节蛋白（RGS）负调控。在人类真菌病原体新型隐球菌中，已鉴定出3个G蛋白α亚基（Gpa1、Gpa2和Gpa3）。在之前的研究中，我们发现RGS蛋白Crg2通过Gpa2和Gpa3参与调节信息素反应途径。在这项研究中，Crg2在控制交配和毒力的Gpa1-cAMP信号通路中发挥了作用。我们发现Crg2与Gpa1物理相互作用，Crg2突变增加cAMP的产生。Crg2突变也增强了交配丝菌丝的产生，但降低了交配过程中细胞间的融合和产孢效率。尽管crg2突变和Gpa1显性活性等位基因GPA1Q284L在正常抑制条件下增强了黑色素的产生，但在小鼠模型中毒力减弱。我们得出结论，Crg2参与控制gpa1 - camp -毒力和信息素-交配信号级联，并假设它可能是这两个中心信号传导管道之间的分子界面。
G proteins orchestrate critical cellular functions by transducing extracellular signals into internal signals and controlling cellular responses to environmental cues. G proteins typically function as switches that are activated by G protein-coupled receptors (GPCRs) and negatively controlled by regulator of G protein signaling (RGS) proteins. In the human fungal pathogen Cryptococcus neoformans, three G protein α subunits (Gpa1, Gpa2, and Gpa3) have been identified. In a previous study, we identified the RGS protein Crg2 involved in regulating the pheromone response pathway through Gpa2 and Gpa3. In this study, a role for Crg2 was established in the Gpa1-cAMP signaling pathway that governs mating and virulence. We show that Crg2 physically interacts with Gpa1 and crg2 mutations increase cAMP production. crg2 mutations also enhance mating filament hyphae production, but reduce cell-cell fusion and sporulation efficiency during mating. Although crg2 mutations and the Gpa1 dominant active allele GPA1Q284L enhanced melanin production under normally repressive conditions, virulence was attenuated in a murine model. We conclude that Crg2 participates in controlling both Gpa1-cAMP-virulence and pheromone-mating signaling cascades and hypothesize it may serve as a molecular interface between these two central signaling conduits.
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影响因子：
3.3
作者：
Bahn, YS;Kojima, K;Heitman, J
通讯作者：
Heitman, J
影响因子：
--
作者：
Hicks, JK;Bahn, YS;Heitman, J
通讯作者：
Heitman, J
影响因子：
3.6
作者：
Han, KH;Seo, JA;Yu, JH
通讯作者：
Yu, JH
影响因子：
3.3
作者：
Lafon, A;Seo, JA;d'Enfert, C
通讯作者：
d'Enfert, C
影响因子：
3.1
作者：
Cox, GM;Mukherjee, J;Perfect, JR
通讯作者：
Perfect, JR