Chromogranin B (secretogranin I), a neuroendocrine‐regulated secretory protein, is sorted to exocrine secretory granules in transgenic mice
Chromogranin B (secretogranin I), a neuroendocrine‐regulated secretory protein, is sorted to exocrine secretory granules in transgenic mice
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Chromogranin B (secretogranin I) 是一种神经内分泌调节的分泌蛋白，在转基因小鼠中被分类为外分泌分泌颗粒
作者：
S. Natori;Angus King;A. Hellwig;U. Weiss;H. Iguchi;B. Tsuchiya;T. Kameya;R. Takayanagi;H. Nawata;W. Huttner
嗜铬粒蛋白B（Cg B，secretogranin I）是一种分泌性颗粒基质蛋白，在多种内分泌细胞和神经元中表达。在这里，我们产生的转基因小鼠表达CgB的人巨细胞病毒启动子的控制下。北方和免疫印迹分析，原位杂交和免疫细胞化学显示，外分泌胰腺的异位CgB表达水平最高的组织。胰腺外分泌的亚细胞分馏后，CgB在各个部分中的分布是无法区分的淀粉酶，内源性成分的酶原颗粒。胰腺腺泡细胞的免疫金电子显微镜检查显示CgB与酶原共定位于高尔基池、浓缩空泡/未成熟颗粒和成熟酶原颗粒中; CgB与酶原的免疫反应性比率在浓缩空泡/未成熟颗粒中最高。从转基因小鼠胰腺酶原颗粒中分离的CgB在体外弱酸性（pH 5.5）环境中聚集，表明低pH诱导的聚集有助于观察到CgB在凝聚空泡中的浓度。我们的研究结果表明，神经内分泌调节的分泌蛋白可以在体内被分选到外分泌分泌颗粒中，这意味着CgB在神经内分泌细胞的trans-Golgi网络中分选的一个关键特征，即其在未成熟分泌颗粒形成过程中的聚集介导的浓度，也发生在外分泌细胞中，尽管认为这些细胞中的分泌蛋白分选主要发生在分泌颗粒成熟过程中。
Chromogranin B (CgB, secretogranin I) is a secretory granule matrix protein expressed in a wide variety of endocrine cells and neurons. Here we generated transgenic mice expressing CgB under the control of the human cytomegalovirus promoter. Northern and immunoblot analyses, in situ hybridization and immunocytochemistry revealed that the exocrine pancreas was the tissue with the highest level of ectopic CgB expression. Upon subcellular fractionation of the exocrine pancreas, the distribution of CgB in the various fractions was indistinguishable from that of amylase, an endogenous constituent of zymogen granules. Immunogold electron microscopy of pancreatic acinar cells showed co‐localization of CgB with zymogens in Golgi cisternae, condensing vacuoles/immature granules and mature zymogen granules; the ratio of immunoreactivity of CgB to zymogens being highest in condensing vacuoles/immature granules. CgB isolated from zymogen granules of the pancreas of the transgenic mice aggregated in a mildly acidic (pH 5.5) milieu in vitro, suggesting that low pH‐induced aggregation contributed to the observed concentration of CgB in condensing vacuoles. Our results show that a neuroendocrine‐regulated secretory protein can be sorted to exocrine secretory granules in vivo, and imply that a key feature of CgB sorting in the trans‐Golgi network of neuroendocrine cells, i.e. its aggregation‐mediated concentration in the course of immature secretory granule formation, also occurs in exocrine cells although secretory protein sorting in these cells is thought to occur largely in the course of secretory granule maturation.
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DOI：
10.1042/bj2990001
发表时间：
1994-04
期刊：
The Biochemical journal
影响因子：
--
作者：
P. Halban;J. Irminger
通讯作者：
P. Halban;J. Irminger
稳定的胰腺酶原颗粒的分离。
DOI：
10.1152/ajpgi.1984.246.4.g411
发表时间：
1984
期刊：
The American journal of physiology
影响因子：
--
作者：
DeLisle,RC;Schulz,I;Tyrakowski,T;Haase,W;Hopfer,U
通讯作者：
Hopfer,U
转基因小鼠的生产。
影响因子：
--
作者：
Gordon,JW
通讯作者：
Gordon,JW
碱性富含脯氨酸的蛋白质的 13 个氨基酸的 N 端结构域对于储存在分泌颗粒中是必需的，并有助于从内质网中排出。
DOI：
--
发表时间：
1992
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Castle,AM;Stahl,LE;Castle,JD
通讯作者：
Castle,JD