Department of Pathology and Laboratory Medicine, Epithelial Pathobiology Research Unit, Emory University, Atlanta, Georgia 30322, USA.
Ann N Y Acad Sci. 2012 Jun;1257:115-24. doi: 10.1111/j.1749-6632.2012.06521.x.
Junctional adhesion molecule-A (JAM-A) is a critical signaling component of the apical junctional complex, a structure composed of several transmembrane and scaffold molecules that controls the passage of nutrients and solutes across epithelial surfaces. Observations from JAM-A-deficient epithelial cells and JAM-A knockout animals indicate that JAM-A is an important regulator of epithelial paracellular permeability; however, the mechanism(s) linking JAM-A to barrier function are not understood. This review highlights recent findings relevant to JAM-A-mediated regulation of epithelial permeability, focusing on the role of upstream and downstream signaling candidates. We draw on what is known about proteins reported to associate with JAM-A in other pathways and on known modulators of barrier function to propose candidate effectors that may mediate JAM-A regulation of epithelial paracellular permeability. Further investigation of pathways highlighted in this review may provide ideas for novel therapeutics that target debilitating conditions associated with barrier dysfunction, such as inflammatory bowel disease.
连接黏附分子-A（JAM-A）是顶端连接复合体的关键信号成分，该复合体由几个跨膜和支架分子组成，控制营养物质和溶质穿过上皮表面的运输。JAM-A 缺陷的上皮细胞和 JAM-A 敲除动物的观察表明，JAM-A 是上皮细胞旁通透性的重要调节剂；然而，将 JAM-A 与屏障功能联系起来的机制尚不清楚。这篇综述重点介绍了与 JAM-A 介导的上皮通透性调节相关的最新发现，关注上游和下游信号候选物的作用。我们借鉴了已知与其他途径中 JAM-A 相关的蛋白质以及已知的屏障功能调节剂的知识，提出了可能介导 JAM-A 调节上皮细胞旁通透性的效应物候选者。对本综述中强调的途径的进一步研究可能为针对与屏障功能障碍相关的致残疾病的新型治疗方法提供思路，如炎症性肠病。
