Amplification of FSH signalling by CFTR and nuclear soluble adenylyl cyclase in the ovary
Amplification of FSH signalling by CFTR and nuclear soluble adenylyl cyclase in the ovary
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DOI：
10.1111/1440-1681.12756
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发表时间：
2017-12-01
影响因子：
2.9
通讯作者：
Chan, Hsiao Chang
中科院分区：
文献类型：
--
作者：
Chen, Hui;Chan, Hsiao Chang
cAMP/PKA信号通路是广泛存在于真核细胞中的重要信号通路之一。经典cAMP/PKA通路的激活依赖于跨膜腺苷酸环化酶（tmAC）。近年来，可溶性腺苷酸环化酶（soluble adenylyl cyclase，sAC）被HCO 3-或Ca 2+激活，成为激活cAMP/PKA通路的另一种途径，而囊性纤维化跨膜传导调节因子（cystic fibrosis transmembrane conductance regulator，CFTR）是cAMP激活的Cl-/HCO 3-传导阴离子通道。本文综述了CFTR/HCO 3依赖的sAC信号转导及其在各种生殖过程中的重要作用，特别是在卵巢功能的调查的新进展。我们提出的证据CFTR/HCO 3-依赖性的核sAC信号级联放大FSH刺激的cAMP/PKA通路，传统上认为涉及tmAC，在颗粒调节雌激素的产生和颗粒细胞增殖。CFTR/HCO 3-/sAC途径在放大其他受体激活的cAMP/PKA信号在各种各样的细胞类型和病理生理过程，包括老化的影响，也进行了讨论。
The cAMP/PKA pathway is one of the most important signalling pathways widely distributed in most eukaryotic cells. The activation of the canonical cAMP/PKA pathway depends on transmembrane adenylyl cyclase (tmAC). Recently, soluble adenylyl cyclase (sAC), which is activated by HCO3- or Ca2+, emerges to provide an alternative way to activate cAMP/PKA pathway with the cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-activated Cl-/HCO3--conducting anion channel, as a key player. This review summarizes new progress in the investigation of the CFTR/HCO3--dependent sAC signalling and its essential role in various reproductive processes, particularly in ovarian functions. We present the evidence for a CFTR/HCO3--dependent nuclear sAC signalling cascade that amplifies the FSH-stimulated cAMP/PKA pathway, traditionally thought to involve tmAC, in granulosa for the regulation of oestrogen production and granulosa cell proliferation. The implication of the CFTR/HCO3-/sAC pathway in amplifying other receptor-activated cAMP/PKA signalling in a wide variety of cell types and pathophysiological processes, including aging, is also discussed.