Role of the GP2/THP Family of GPI‐Anchored Proteins in Membrane Trafficking During Regulated Exocrine Secretion
Role of the GP2/THP Family of GPI‐Anchored Proteins in Membrane Trafficking During Regulated Exocrine Secretion
复制标题
GPI 锚定蛋白 GP2/THP 家族在调节外分泌分泌过程中膜运输中的作用
作者：
G. Scheele;S. Fukuoka;S. Freedman
与顶端分泌膜相关的GPY锚定膜蛋白的GPY THP家族的鉴定和表征表明，这类新的GPI连接蛋白在胰腺、肝、肺、肾和胃肠道的极化上皮细胞中调节蛋白质分泌和离子转运中起关键作用。根据最近从世界文献和我们自己的调查中获得的信息，我们提出了以下两个假设，能够统一以前的各种观察。假设1是在反式高尔基体网络（trans-Golgi network，TGN）的酸性环境中形成的GP 2四聚体组织了与酶原颗粒（ZG）膜的腔表面紧密结合的GP 2蛋白聚糖（PG）基质，并提出该基质在（a）TGN中颗粒组装期间的膜分选，（B）分泌储存阶段期间ZG膜的失活，和（c）胞吐后ZG膜从顶端质膜（APM）的调节运输。假设2是腺泡腔构成了一个独特的生理隔室，用于腺泡和导管细胞之间的耦合生化反应。由于TGN的酸性pH在分泌蛋白的凝聚中起关键作用，因此需要腺泡腔的碱化来（a）中和胞吐内容物的酸性pH和（B）溶解聚集的（原）酶。进一步碱化似乎需要pH依赖性释放的GP 2/PG矩阵从APM，一个过程，可以调节ZG膜的内化，在分泌过程中重复使用。两者合计，这两个假设表明，管腔因素，包括酸碱相互作用和基质组装和拆卸过程中执行的关键功能，在调节储存和释放的胰腺（原）酶。耦合反应的要求，通过不同的上皮细胞（腺泡细胞和导管细胞）上的单独的激素[胆囊收缩素（CCK）和分泌素]的行动进行协调，提供了一个新的认识，结合CCK和分泌素刺激的重要性，在胰腺分泌的食物摄入。
Identification and characterization of the GPY THP family of GPI-anchored membrane proteins associated with apical secretory membranes suggest that this new class of GPI-linked proteins plays a critical role in regulated protein secretion and ion transport in polarized epithelial cells in pancreas, liver, lung, kidney, and gastrointestinal tract. Based on recent information obtained from the world literature and from our own investigations we present the following two hypotheses capable of unifying previously diverse observations. Hypothesis 1 is that formation of GP2 tetramers in the acidic milieu of the trans-Golgi network (TGN) organizes a GP2iproteoglycan (PG) matrix tightly associated with the luminal surface of zymogen granule (ZG) membranes, and proposes that this matrix functions in (a) membrane sorting during granule assembly in the TGN, (b) inactivation of ZG membranes during the storage phase of secretion, and (c) regulated trafficking of ZG membranes from the apical plasma membrane (APM) after exocytosis. Hypothesis 2 is that the acinar lumen constitutes a distinct physiologic compartment for coupled biochemical reactions between acinar and duct cells. Because the acidic pH of the TGN plays a critical role in condensation of secretory proteins, alkalinization of the acinar lumen is required for (a) neutralization of the acidic pH of exocytic contents and (b) solubilization of aggregated (pro)enzymes. Further alkalinization appears to be required for pH-dependent release of the GP2/PG matrix from the APM, a process that may regulate internalization of ZG membranes for reuse during secretion. Taken together, the two hypotheses suggest that luminal factors including acid-base interactions and matrix assembly and disassembly processes perform critical functions during regulated storage and release of pancreatic (pro)enzymes. The requirement that coupling reactions be coordinated through the actions of separate hormones [cholecystokinin (CCK) and secretin] on divergent epithelial cells (acinar and duct cells, respectively) provides a new appreciation for the importance of combined CCK and secretin stimulation during pancreatic secretion in response to food intake.
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
DOI：
10.1016/s0021-9258(18)77318-3
发表时间：
1990-08
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
S. Yoo;J. Albanesi
通讯作者：
S. Yoo;J. Albanesi
从大鼠正常和肿瘤性胰腺腺泡细胞中分离的分泌颗粒的分泌蛋白和膜组成的比较。
DOI：
10.1073/pnas.80.14.4379
发表时间：
1983
影响因子：
11.1
作者：
Hansen,LJ;Reddy,MK;Reddy,JK
通讯作者：
Reddy,JK