Dillen L, Miserez B, Claeys M, Aunis D, De Potter W
Department of Pharmaceutical Sciences, University of Antwerp, UIA, Belgium.
Neurochem Int. 1993 Apr;22(4):315-52. doi: 10.1016/0197-0186(93)90016-x.
Posttranslational processing of peptide-precursors is nowadays believed to play an important role in the functioning of neurons and endocrine cells. Both proenkephalins and chromogranins/secretogranins are considered as precursor molecules in these tissues, resulting in posttranslationally formed degradation products with potential biological activities. Among the proteins and peptides of neuronal and endocrine secretory granules, the enkephalins and enkephalin-containing peptides have been most extensively studied. The characterization of the post-translationally formed degradation products of the proenkephalins have enabled the understanding of their processing pathway. Chromogranins/secretogranins represent a group of acidic glycoproteins, contained within hormone storage granules. The biochemistry, biogenesis and molecular properties of these proteins have already been studied for 25 years. The chromogranins/secretogranins have a widespread distribution throughout the neuroendocrine system, the adrenal medullary chromaffin granules being the major source of these storage components. Recent data provide evidence for a precursor role for all members of the chromogranins/secretogranins family although also several other functions have been proposed. In this review, some of the methods applied to study proteolytic processing are described. In addition, the posttranslational processing of chromogranins/secretogranins and proenkephalins, especially the biochemical aspects, will be discussed and compared. Recent exciting developments on the generation and identification of potential physiologically active fragments will be covered.
如今,人们认为肽前体的翻译后加工在神经元和内分泌细胞的功能中起着重要作用。前脑啡肽原和嗜铬粒蛋白/分泌粒蛋白都被视为这些组织中的前体分子,会产生具有潜在生物活性的翻译后形成的降解产物。在神经元和内分泌分泌颗粒的蛋白质和肽类中,脑啡肽和含脑啡肽的肽类研究最为广泛。前脑啡肽原翻译后形成的降解产物的特性使得人们能够了解其加工途径。嗜铬粒蛋白/分泌粒蛋白是一组酸性糖蛋白,存在于激素储存颗粒中。这些蛋白质的生物化学、生物发生和分子特性已经研究了25年。嗜铬粒蛋白/分泌粒蛋白在整个神经内分泌系统中广泛分布,肾上腺髓质嗜铬颗粒是这些储存成分的主要来源。最近的数据为嗜铬粒蛋白/分泌粒蛋白家族所有成员的前体作用提供了证据,不过也有人提出了其他一些功能。在这篇综述中,描述了一些用于研究蛋白水解加工的方法。此外,还将讨论和比较嗜铬粒蛋白/分泌粒蛋白和前脑啡肽原的翻译后加工,尤其是生物化学方面。还将介绍潜在生理活性片段的产生和鉴定方面的最新激动人心的进展。