Laboratory of Physiology, Department of Marine Bioscience, Atmosphere and Ocean Research Institute, The University of Tokyo, Kashiwa, Chiba 277-8564, Japan.
Gen Comp Endocrinol. 2022 Jan 1;315:113797. doi: 10.1016/j.ygcen.2021.113797. Epub 2021 May 3.
Guanylyl cyclase (GC) is an enzyme that produces 3',5'-cyclic guanosine monophosphate (cGMP), one of the two canonical cyclic nucleotides used as a second messenger for intracellular signal transduction. The GCs are classified into two groups, particulate/membrane GCs (pGC) and soluble/cytosolic GCs (sGC). In relation to the endocrine system, pGCs include hormone receptors for natriuretic peptides (GC-A and GC-B) and guanylin peptides (GC-C), while sGC is a receptor for nitric oxide and carbon monoxide. Comparing the functions of pGCs in eukaryotes, it is apparent that pGCs perceive various environmental factors such as light, temperature, and various external chemical signals in addition to endocrine hormones, and transmit the information into the cell using the intracellular signaling cascade initiated by cGMP, e.g., cGMP-dependent protein kinases, cGMP-sensitive cyclic nucleotide-gated ion channels and cGMP-regulated phosphodiesterases. Among vertebrate pGCs, GC-E and GC-F are localized on retinal epithelia and are involved in modifying signal transduction from the photoreceptor, rhodopsin. GC-D and GC-G are localized in olfactory epithelia and serve as sensors at the extracellular domain for external chemical signals such as odorants and pheromones. GC-G also responds to guanylin peptides in the urine, which alters sensitivity to other chemicals. In addition, guanylin peptides that are secreted into the intestinal lumen, a pseudo-external environment, act on the GC-C on the apical membrane for regulation of epithelial transport. In this context, GC-C and GC-G appear to be in transition from exocrine pheromone receptor to endocrine hormone receptor. The pGCs also exist in various deuterostome and protostome invertebrates, and act as receptors for environmental, exocrine and endocrine factors including hormones. Tracing the evolutionary history of pGCs, it appears that pGCs first appeared as a sensor for physicochemical signals in the environment, and then evolved to function as hormone receptors. In this review, the author proposes an evolutionary history of pGCs that highlights the emerging role of the GC/cGMP system for signal transduction in hormone action.
鸟苷酸环化酶（GC）是一种酶，可产生 3'，5'-环鸟苷酸（cGMP），这是两种经典的环核苷酸之一，用作细胞内信号转导的第二信使。GC 分为两组，颗粒/膜 GC（pGC）和可溶性/胞质 GC（sGC）。就内分泌系统而言，pGC 包括利钠肽（GC-A 和 GC-B）和鸟苷素肽（GC-C）的激素受体，而 sGC 是一氧化氮和一氧化碳的受体。比较真核生物中 pGC 的功能，显然 pGC 除了内分泌激素外，还感知各种环境因素，如光、温度和各种外部化学信号，并通过 cGMP 引发的细胞内信号级联将信息传递到细胞内，例如 cGMP 依赖性蛋白激酶、cGMP 敏感的环核苷酸门控离子通道和 cGMP 调节的磷酸二酯酶。在脊椎动物 pGC 中，GC-E 和 GC-F 位于视网膜上皮细胞中，参与调节来自光感受器视紫红质的信号转导。GC-D 和 GC-G 位于嗅觉上皮细胞中，作为细胞外化学信号（如气味和信息素）的传感器在细胞外结构域发挥作用。GC-G 还对尿液中的鸟苷素肽做出反应，从而改变对其他化学物质的敏感性。此外，分泌到肠腔（假性外环境）的鸟苷素肽作用于顶膜上的 GC-C，以调节上皮转运。在这种情况下，GC-C 和 GC-G 似乎正在从外分泌信息素受体向内分泌激素受体转变。pGC 也存在于各种后口动物和原口动物无脊椎动物中，作为环境、外分泌和内分泌因子（包括激素）的受体发挥作用。追踪 pGC 的进化历史，似乎 pGC 首先作为环境中物理化学信号的传感器出现，然后进化为激素受体的功能。在这篇综述中，作者提出了 pGC 的进化历史，强调了 GC/cGMP 系统在激素作用的信号转导中新兴的作用。
