Membrane domains and macromolecular transport in intestinal epithelial cells.
Membrane domains and macromolecular transport in intestinal epithelial cells.
复制标题
肠上皮细胞的膜结构域和大分子运输。
DOI：
10.1164/ajrccm/138.6_pt_2.s10
复制
发表时间：
1988
期刊：
影响因子：
--
通讯作者：
Kraehenbuhl,JP
中科院分区：
文献类型：
--
作者：
Neutra,MR;Wilson,JM;Weltzin,RA;Kraehenbuhl,JP
上皮细胞质膜被组织为生化和功能上不同的域和子域。我们探索了肠上皮特化细胞内吞作用和跨上皮囊泡运输过程中特定膜区域的组成和维持。在乳鼠回肠吸收细胞的顶端内吞亚结构域和内体小管中发现了一种独特的膜糖蛋白。该内吞系统参与肽生长因子的分选和跨上皮转运以及将乳大分子递送至溶酶体。在滤泡相关上皮的 M 细胞中，我们发现膜结合蛋白被有效地转运到基底外侧膜的特殊亚结构域。这些细胞的顶膜具有免疫球蛋白结合位点并将单克隆IgA抗体转运至基底外侧，在那里它们可以与粘膜免疫系统的细胞相互作用。 AM 修订版 RE5PIR DI5 1988 年； 138: 510-516 极化上皮细胞的质膜被组织为由带状膜内屏障（紧密连接）分隔的两个主要域。这些结构域的蛋白质组成存在显着差异，这些差异已在肠道吸收细胞中得到证实 (1, 2)，其中高度特化的顶端结构域面向肠腔，而基底外侧结构域暴露于间质液。最近对培养的上皮单层（主要是 MDCK 细胞）中膜蛋白分选的研究表明，不同结构域的维持不仅取决于连接屏障，还取决于基底外侧表面与细胞外底物的相互作用 (3-6)。除了细胞基质接触之外，细胞与细胞接触似乎还提供了将含有顶膜成分的囊泡正确递送至非接触域所必需的细胞内组织 (7)。目前正在使用分子克隆和细胞转染方法研究可能将膜内和分泌蛋白“定位”到两个主要结构域的分子特征，并已在其他地方进行了综述(8-10)。人们很少关注主要领域内存在的不同成分的特殊膜区域。例如，柱状上皮细胞的“基底外侧”表面包括与相邻上皮细胞相互作用的侧表面和与基底层的细胞外基质(ECM)成分相互作用的基底表面。已知某些细胞的侧膜富含细胞间粘附分子 (II, 12)，并且基底表面预计含有一定浓度的 ECM 受体。我们观察到，在肠和其他上皮细胞中，Na,K-ATP 酶主要集中在侧质膜中，并且很大程度上被排除在基底亚结构域之外 (13)。这种膜内异二聚体与膜下细胞骨架关联，有人认为这种关联可能将其引导至基底外侧结构域，并可能将其固定在适当的位置 (14)。特定的膜相关蛋白聚糖也集中在各种上皮细胞的外侧亚结构域中 (15)。目前尚不清楚这些子域在组成上还有哪些其他方面存在差异，也不知道在它们之间不存在连接屏障的情况下如何保持这些差异。
Epithelial cell plasma membranes are organized as biochemically and functionally distinct domains and subdomains. We have explored the composition and maintenance of specific membrane regions during endocytosis and transepithelial vesicular transport in specialized cells of the intestinal epithelium. A unique membrane glycoprotein has been identified in apical endocytic subdomains and endosomal tubules of absorptive cells in suckling rat ileum. This endocytic system is involved in sorting and transepithelial transport of peptide growth factors as well as delivery of milk macromolecules to Iysosomes. In M cells of follicle-associated epithelium, we have shown that membrane-bound proteins are efficiently transported to a specialized subdomain of basolateral membrane. The apical membranes of these cells bear immunoglobulin binding sites and transport monoclonallgA antibodies to the basolateral side, where they may interact with cells of the mucosal immune system. AM REV RE5PIR DI5 1988; 138: 510-516The plasma membranes of polarized epithelial cells are organized as two major domains separated by a belt-like intramembrane barrier, the tight junction. Dramatic differences in the protein composition of these domains have been documented in intestinal absorptive cells (1, 2), where a highly specialized apical domain faces the intestinal lumen while the basolateral domain is exposed to interstitial fluid. Recent studies on membrane protein sorting in cultured epithelial monolayers, primarily MDCK cells, indicate that maintenance of distinct domains depends not only on the junctional barrier but also on the interaction of basolateral surfaces with extracellular substrates (3-6). In addition to cellsubstrate contact, cell-cellcontacts appear to provide the intracellular organization necessary for correct delivery of vesicles containing apical membrane components to the noncontacting domain (7). The molecular features that may" address" intramembrane and secretory proteins to the two major domains are currently under study using molecular cloning and cell transfection methods and have been reviewed elsewhere (8-10). Less attention has been focused on the specialized membrane regions of distinct compositions that existwithin major domains. For example, the" basolateral" surface of a columnar epithelial cellincludes lateral surfaces that interact with adjacent epithelial cells and a basal surface that interacts with extracellular matrix (ECM) components of the basal lamina. Lateral membranes of some cells are known to be enriched in cell-cell adhesion molecules (II, 12), and basal surfaces are expected to contain a concentration of receptors for ECM. We have observed that in intestinal and other epithelial cells, Na, K-ATPase is concentrated primarily in lateral plasma membranes and is largely excluded from the basal subdomain (13). This intramembrane heterodimer associates with the submembrane cytoskeleton, and it has been suggested that this association may direct it to the basolateral domain and perhaps tether it in place (14). Specificmembrane-associated proteoglycans are also concentrated in the lateral subdomain of various epithelial cells (15). It is not known in what other respects these subdomains differ in composition or exactly how such differences are maintained in the absence of a junctional barrier between them.