Hendy G N, Bevan S, Mattei M G, Mouland A J
Calcium Research Laboratory, McGill University, Montreal, Quebec.
Clin Invest Med. 1995 Feb;18(1):47-65.
Chromogranin A (CgA) is the major member of the granin family of acidic secretory glycoproteins that are expressed in all endocrine and neuroendocrine cells. Granins have been proposed to play multiple roles in the secretory process. Intracellularly, granins play a role in targeting peptide hormones and neurotransmitters to granules of the regulated pathway by virtue of their ability to aggregate in the low-pH, high-calcium environment of the trans-Golgi network. Extra-cellularly, peptides formed as a result of proteolytic processing of granins regulate hormone secretion. Some conserved features of the mature CgA protein are polyglutamic acids, calcium-binding sites, and several pairs of basic amino acids. The first 2 features are important for its intracellular functions, and the latter characteristic suggested that peptides could be released from the molecule by precursor processing enzymes. Several biologically active peptides encoded within the CgA molecule, such as vasostatin, beta-granin, chromostatin, pancreastatin, and parastatin act predominantly to inhibit hormone and neurotransmitter release in an autocrine or paracrine fashion. The biosynthesis of CgA is regulated by many different factors, including steroid hormones and agents that act through a variety of signalling pathways. CgA biosynthesis and that of the resident hormone or neurotransmitter can be regulated differentially. The widespread distribution of CgA has made the measurement of circulating immunoreactive CgA a valuable tool in the diagnosis of neuroendocrine neoplasia, and CgA immunohistochemistry can help to identify the neuroendocrine nature of tumours. Recent molecular biology studies are identifying those elements in the CgA gene promoter responsible for its specific neuroendocrine cell expression.
嗜铬粒蛋白A（CgA）是酸性分泌糖蛋白颗粒素家族的主要成员，在所有内分泌和神经内分泌细胞中均有表达。颗粒素被认为在分泌过程中发挥多种作用。在细胞内，颗粒素凭借其在反式高尔基体网络低pH、高钙环境中聚集的能力，在将肽类激素和神经递质靶向调节性途径的颗粒方面发挥作用。在细胞外，颗粒素经蛋白水解加工形成的肽调节激素分泌。成熟CgA蛋白的一些保守特征包括多聚谷氨酸、钙结合位点以及几对碱性氨基酸。前两个特征对其细胞内功能很重要，后一个特征表明肽可通过前体加工酶从该分子中释放出来。CgA分子内编码的几种生物活性肽，如血管抑素、β-颗粒素、嗜铬粒抑制素、胰腺抑制素和甲状旁腺抑制素，主要以自分泌或旁分泌方式抑制激素和神经递质的释放。CgA的生物合成受许多不同因素调节，包括类固醇激素和通过多种信号通路起作用的因子。CgA的生物合成与驻留激素或神经递质的生物合成可受到不同调节。CgA的广泛分布使得检测循环中的免疫反应性CgA成为神经内分泌肿瘤诊断中的一种有价值工具，并且CgA免疫组织化学有助于识别肿瘤的神经内分泌性质。最近的分子生物学研究正在确定CgA基因启动子中负责其在特定神经内分泌细胞中表达的那些元件。
