Secretory component: the polymeric immunoglobulin receptor. What's in it for the gastroenterologist and hepatologist?
Secretory component: the polymeric immunoglobulin receptor. What's in it for the gastroenterologist and hepatologist?
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分泌成分：聚合免疫球蛋白受体。
DOI：
10.1016/0016-5085(85)90467-6
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发表时间：
1985
期刊：
影响因子：
29.4
通讯作者：
Kloppel,TM
中科院分区：
文献类型：
--
作者：
Ahnen,DJ;Brown,WR;Kloppel,TM
SC-pIg 系统的主要功能是将 pIg 分泌到各种外部分泌物中。负责这种运输的细胞机制如图5所示。聚合免疫球蛋白A由属于粘膜相关淋巴组织一部分的浆细胞合成，通过从粘膜合成位点扩散进入上皮细胞白蛋白表面的SC，或进入血液循环，并主要通过肝脏转运进入胆汁中清除。 pIgA 最初通过可饱和、可逆且对 pIgA 和 IgM 具有特异性的非共价相互作用与上皮细胞（可能还有肝细胞）近腔表面上的 SC 结合。随后，SC 与其配体之间的共价相互作用在不同物种中发生程度不同。 SC-IgA复合物被上皮细胞或肝细胞内吞，并通过微管依赖性囊泡转运机制跨细胞转运至外部分泌物中。在运输过程中的某个时刻，复合物通过膜相关 SC 分子的蛋白水解裂解而变得可溶，从而将可溶性 sIgA 释放到腺腔或小管中。在肠腔中，SC 有助于保护 sIgA 分子免遭蛋白水解降解。 sIgA 可能在针对病原微生物或有害抗原的粘膜防御中发挥重要作用。SC-pIg 系统在几个重要方面不同于许多其他已知的受体-配体相互作用。首先，受体（SC）的合成或表达，或两者，不受配体浓度的调节。其次，SC 可能不会与其配体解离或循环到细胞表面，因为它与其配体 (pIg) 复合物分泌到外部分泌物中。第三，pIgs与其受体的相互作用并不起到调节细胞内过程的作用，而是导致配体的跨细胞转运，该配体在外部环境中起作用。第四，在受体与其配体之间最初的非共价、可逆结合之后，通过在 SC 和 pIg 之间形成二硫键，相互作用变为共价。最后，SC最初作为整合膜蛋白插入上皮细胞的近腔结构域，随后通过蛋白水解裂解成由细胞分泌的可溶性分子。因此，与许多细胞表面受体-配体相互作用（配体最终被降解而受体被保守）相反，SC-pIgA相互作用导致受体部分蛋白水解降解和配体保守。尽管已经积累了有关该受体-配体系统的丰富信息，但仍有许多非常重要的问题有待回答：SC在肠和肝脏等组织中的合成和表达是如何调节的？是什么决定了 SC 在正常分化过程中的表达方式？负责将膜 SC 分类到质膜的近腔域，然后将 SC 重新路由到并通过腔质膜的细胞机制是什么？ SC-pIg 跨细胞转运途径在何处以及如何与其他受体介导的内吞途径不同？ sIgA或分泌型IgM分泌到细胞外环境后有哪些具体功能？从肝脏和消化器官的病理生理学角度来看，对SC和SC-pIg相互作用的充分了解可能将极大地有助于理解肝细胞和肠上皮细胞的细胞生物学的许多基本方面。此外，有关主要发病机制的重要线索......
The primary function of the SC-pIg system is to secrete pIgs into various external secretions. The cellular mechanism responsible for this transport is schematically depicted in Figure 5. Polymeric immunoglobulin A, which is synthesized by plasma cells that are part of the mucosa-associated lymphoid tissue, gains access to the SC on the albuminal surface of epithelial cells by diffusion from sites of synthesis in mucosae or enters the blood circulation and is cleared, largely by hepatic transport, into bile. The pIgA binds to SC on the abluminal surface of the epithelial cells (and probably hepatocytes) initially by noncovalent interactions that are saturable, reversible, and specific for pIgA and IgM. Subsequently, covalent interaction between SC and its ligand occurs to a variable degree in different species. The SC-IgA complex is endocytosed by the epithelial cell or hepatocyte and is transported across the cell into the external secretions by a microtubule-dependent vesicular transport mechanism. At some point during the transport, the complex is rendered soluble by proteolytic cleavage of the membrane-associated SC molecule to release the soluble sIgA into the gland lumen or the canaliculus. In the intestinal lumen, SC helps protect the sIgA molecule from proteolytic degradation. The sIgA may play a major role in the mucosal defense against pathogenic organisms or harmful antigens.The SC-pIg system differs from many of the other known receptor-ligand interactions in several important ways. First, the synthesis or expression of the receptor (SC), or both, are not regulated by the concentration of the ligand. Second, SC probably is not dissociated from its ligand or recycled to the cell surface as it is secreted in complex with its ligand (pIg) into the external secretions. Third, the interaction of pIgs with their receptor does not function to regulate an intracellular process, but results in transcellular transport of the ligand, which acts in the external environment. Fourth, after initial noncovalent, reversible binding between the receptor and its ligand, the interaction becomes covalent by the formation of disulfide linkages between SC and the pIg. Finally, SC is initially inserted into the abluminal domain of epithelial cells as an integral membrane protein and subsequently is proteolytically cleaved to a soluble molecule which is secreted by the cell. Thus, in contrast to many cell-surface receptor-ligand interactions in which the ligand is ultimately degraded and the receptor is conserved, the SC-pIgA interaction results in partial proteolytic degradation of the receptor and conservation of the ligand.Despite the wealth of information that has accumulated about this receptor-ligand system, a number of very important questions remain to be answered: How is the synthesis and expression of SC in tissues such as the intestine and the liver regulated? What determines how SC is expressed during normal differentiation? What are the cellular mechanisms responsible for the sorting of membrane SC to the abluminal domain of the plasma membrane and then rerouting of SC to and through the luminal plasma membrane? Where and how does the SC-pIg transcellular transport pathway diverge from other receptor-mediated endocytic pathways? What are the specific functions of the sIgA or secretory IgM after secretion into the extracellular environment?From the standpoint of pathophysiology of the liver and digestive organs, it is likely that full understanding of SC and SC-pIg interactions will greatly contribute to understanding of many fundamental aspects of the cellular biology of hepatocytes and intestinal epithelial cells. Moreover, important clues concerning the pathogenesis of major …
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