Condensation-sorting events in the rough endoplasmic reticulum of exocrine pancreatic cells.
Condensation-sorting events in the rough endoplasmic reticulum of exocrine pancreatic cells.
复制标题
DOI：
10.1083/jcb.109.1.35
复制
发表时间：
1989-07
期刊：
影响因子：
--
通讯作者：
Howell KE
中科院分区：
文献类型：
--
作者：
Tooze J;Kern HF;Fuller SD;Howell KE
在豚鼠的胰腺外分泌细胞中，脑池内颗粒（ICG）以低频率出现在粗面内质网腔内。通过饥饿和重新喂养豚鼠或将其注射到CoCl 2溶液中，这些颗粒的数量大大增加。我们在这里显示，ICGs包含一套完整的分泌胰腺消化酶和酶原。RER内腔中的另外两种可溶性蛋白质，GRP 78/BiP和蛋白质二硫化物异构酶（PDI），被明确排除在ICG之外。因此，ICG的形成是一个分选事件，涉及一套完整的分泌酶和酶原的共缩合，为简洁起见，我们统称为酶原。除了约50%的RNA酶外，ICG中的酶原通过分子间二硫键共价交联。所有三种常驻ER池蛋白-PDI、GRP 78/BiP和GRP 94-与羧基末端序列KDEL的合成是响应于RER内腔中ICG中大量错误折叠分泌蛋白的积累而诱导的。大鼠注射大剂量的对氯苯丙氨酸甲酯后，粗面内质网腔内形成晶体。我们表明，这些晶体似乎是淀粉酶的晶格，层与层之间掺入了其他酶原。从这些晶体中排除了GRP 78/BiP和PDI。因此，粗面内质网内淀粉酶晶体的形成和其他酶原的加入也是一个分选过程。这些数据表明，在胰腺外分泌细胞中，酶原可以在RER中共凝聚成无定形聚集体或排除其他可溶性RER蛋白的晶体。这表明共缩合是一种能够在分泌途径内分选酶原的机制。
In guinea pig exocrine pancreatic cells intracisternal granules (ICGs) occur at a low frequency within the lumen of the RER. By starving and refeeding guinea pigs or injecting them in CoCl2 solution, the number of these granules is greatly increased. We show here that ICGs contain the complete set of secreted pancreatic digestive enzymes and proenzymes. Two other soluble proteins in the lumen of the RER, GRP 78/BiP and protein disulphide isomerase (PDI), are specifically excluded from ICGs. The formation of ICGs, which occurs without acidification of the RER cisternae, is therefore a sorting event involving the cocondensation of a complete set of secretory enzymes and proenzymes, which for brevity we refer to collectively as the zymogens. With the exception of approximately 50% of the RNase, the zymogens in ICGs are covalently cross-linked by intermolecular disulphide bonds. The synthesis of all three resident ER cisternal proteins--PDI, GRP 78/BiP, and GRP 94--with the carboxy-terminal sequence KDEL, is induced in response to the accumulation of massive amounts of misfolded secretory protein in the ICGs in the lumen of the RER. After injection of rats with large doses of parachlorophenylalanine-methylester, crystals form in the lumen of the RER. We show that these crystals appear to be a lattice of amylase with the other zymogens incorporated between the layers. Both GRP 78/BiP and PDI are excluded from these crystals. The formation of these amylase crystals within the RER and the inclusion of other zymogens is, therefore, also a sorting event. These data establish that in exocrine pancreatic cells zymogens can cocondense in the RER into either amorphous aggregates or crystals that exclude other soluble RER proteins. This demonstrates that cocondensation is a mechanism capable of sorting zymogens within the secretory pathway.