The cAMP pathway is important for controlling the morphological switch to the pathogenic yeast form of Paracoccidioides brasiliensis.
The cAMP pathway is important for controlling the morphological switch to the pathogenic yeast form of Paracoccidioides brasiliensis.
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DOI：
10.1111/j.1365-2958.2007.05824.x
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发表时间：
2007-08
影响因子：
3.6
通讯作者：
Borges-Walmsley, M Ines
中科院分区：
文献类型：
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作者：
Chen, Daliang;Janganan, Thamarai K;Chen, Gongyou;Marques, Everaldo R;Kress, Marcia R;Goldman, Gustavo H;Walmsley, Adrian R;Borges-Walmsley, M Ines
巴西副球孢子菌是一种人类致病真菌，它从腐生菌丝体转变为致病酵母。与受 cAMP 信号通路调节的形态转变一致，细胞 cAMP 水平在向酵母形态转变的开始（< 24 小时）和后期（> 120 小时）均短暂增加，并且这种转变可以通过外源 cAMP 调节。我们克隆了编码腺苷酸环化酶 (AC) 的 cyr1 基因，并确定其转录水平与 cAMP 水平相关。此外，我们还克隆了编码三种 Gα (Gpa1-3)、Gβ (Gpb1) 和 Gγ (Gpg1) G 蛋白的基因。 Gpa1 和 Gpb1 彼此以及 AC 的 N 末端相互作用，但 Gpa2 和 Gpa3 都不与 Gpb1 或 AC 相互作用。 Gpa1 与 Gpb1 的相互作用被 GTP 阻断，但其与 AC 的相互作用与结合的核苷酸无关。菌丝体中 gpa1、gpb1 和 gpg1 的转录水平相似，但在转变过程中 gpb1 短暂过量，而酵母中 gpa1 过量。我们用一种新的信号传导机制解释了我们的发现，其中 AC 的活性受到 Gpa1 和 Gpb1 的差异调节，以在形态转换所需的 10 天内维持信号。
Paracoccidioides brasiliensis is a human pathogenic fungus that switches from a saprobic mycelium to a pathogenic yeast. Consistent with the morphological transition being regulated by the cAMP-signalling pathway, there is an increase in cellular cAMP levels both transiently at the onset (< 24 h) and progressively in the later stages (> 120 h) of the transition to the yeast form, and this transition can be modulated by exogenous cAMP. We have cloned the cyr1 gene encoding adenylate cyclase (AC) and established that its transcript levels correlate with cAMP levels. In addition, we have cloned the genes encoding three Gα (Gpa1–3), Gβ (Gpb1) and Gγ (Gpg1) G proteins. Gpa1 and Gpb1 interact with one another and the N-terminus of AC, but neither Gpa2 nor Gpa3 interacted with Gpb1 or AC. The interaction of Gpa1 with Gpb1 was blocked by GTP, but its interaction with AC was independent of bound nucleotide. The transcript levels for gpa1, gpb1 and gpg1 were similar in mycelium, but there was a transient excess of gpb1 during the transition, and an excess of gpa1 in yeast. We have interpreted our findings in terms of a novel signalling mechanism in which the activity of AC is differentially modulated by Gpa1 and Gpb1 to maintain the signal over the 10 days needed for the morphological switch.