Department of Integrative Biology, University of Guelph, Ontario, Canada.
Endocrinology. 2012 Nov;153(11):5440-51. doi: 10.1210/en.2012-1677. Epub 2012 Sep 13.
Glycoprotein hormones (GPHs) comprise a group of signaling molecules critical for major metabolic and reproductive functions. In vertebrates they include chorionic gonadotropin, LH, FSH, and TSH. The active hormones are characterized by heterodimerization between a common α and hormone-specific β subunit, which activate leucine-rich repeat-containing G protein coupled receptors. To date, genes referred to as GPHα2 and GPHβ5 have been the only glycoprotein hormone subunits identified in invertebrates, suggesting that other GPHα and GPHβ subunits diversified during vertebrate evolution. Still the functions of GPHα2 and GPHβ5 remain largely unknown for both vertebrates and invertebrates. To further understand the evolution and putative function of these subunits, we cloned and analyzed phylogenetically two glycoprotein subunits, AcaGPHα and AcaGPHβ, from the sea hare Aplysia californica. Model based three-dimensional predictions of AcaGPHβ confirm the presence of a complete cysteine knot, two hairpin loops, and a long loop. As in the human GPHβ5 subunit the seatbelt structure is absent in AcaGPHβ. We also found that AcaGPHα and AcaGPHβ subunits are expressed in larval stages of Aplysia, and we present a detailed expression map of the subunits in the adult central nervous system using in situ hybridizations. Both subunits are expressed in subpopulations of pleural and buccal mechanosensory neurons, suggesting a neuronal modulatory function of these subunits in Aplysia. Furthermore it supports the model of a relatively diffuse neuroendocrine-like system in molluscs, where specific primary sensory neurons release peptides extrasynaptically (paracrine secretion). This is in contrast to vertebrates and insects, in which releasing and stimulating factor from centralized sensory regions of the central nervous system ultimately regulate hormone release in peripheral glands.
糖蛋白激素（GPHs）是一组对主要代谢和生殖功能至关重要的信号分子。在脊椎动物中，它们包括绒毛膜促性腺激素、LH、FSH 和 TSH。活性激素的特征是由共同的α和激素特异性的β亚基组成的异二聚体，它们激活富含亮氨酸重复的 G 蛋白偶联受体。迄今为止，被称为 GPHα2 和 GPHβ5 的基因是唯一在无脊椎动物中鉴定出的糖蛋白激素亚基，这表明其他 GPHα 和 GPHβ 亚基在脊椎动物进化过程中多样化。然而，GPHα2 和 GPHβ5 的功能对于脊椎动物和无脊椎动物来说仍然很大程度上未知。为了进一步了解这些亚基的进化和可能的功能，我们从加利福尼亚海兔 Aplysia californica 中克隆和分析了两种糖蛋白亚基，AcaGPHα 和 AcaGPHβ，并进行了系统发育分析。基于模型的 AcaGPHβ 三维预测证实了完整的半胱氨酸结、两个发夹环和一个长环的存在。与人类 GPHβ5 亚基一样，AcaGPHβ 中不存在安全带结构。我们还发现 AcaGPHα 和 AcaGPHβ 亚基在 Aplysia 的幼虫阶段表达，并使用原位杂交技术呈现了亚基在成年中枢神经系统中的详细表达图谱。这两个亚基都在胸神经节和颊神经节机械感觉神经元的亚群中表达，这表明这些亚基在 Aplysia 中具有神经元调节功能。此外，这支持了在软体动物中存在相对弥散的神经内分泌样系统的模型，其中特定的初级感觉神经元在突触外释放肽（旁分泌分泌）。这与脊椎动物和昆虫形成对比，在脊椎动物和昆虫中，来自中枢神经系统中央感觉区域的释放和刺激因子最终调节外周腺体中的激素释放。
