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作 者:张世佳 郑娟霞 王琤 ZHANG Shi-Jia;ZHENG Juan-Xia;WANG Cheng-Wei(College of Life Science,Jiangxi Science and Technology Normal University,Nanchang 330013,China;Guixi Experimental Middle School,Guixi 335400,China)
机构地区:[1]江西科技师范大学生命科学学院,南昌330013 [2]贵溪市实验中学,贵溪335400
出 处:《生物化学与生物物理进展》2024年第11期2832-2844,共13页Progress In Biochemistry and Biophysics
基 金:国家自然科学基金(32260850)资助项目。
摘 要:紧密连接(tight junction,TJ)是存在于上皮细胞之间或上皮细胞与内皮细胞之间的细胞连接,也是维持机体各种屏障结构的基础,在物质通过旁细胞通路转运过程中起栅栏和屏障作用,控制着物质跨膜运输及维持细胞极性。闭合蛋白(occludin)是紧密连接相关蛋白中最具有代表性的蛋白质之一,在TJ的组装、稳定性和屏障功能中发挥重要作用,它的表达和调控会影响多种疾病的发生。本文旨在综述occludin的结构、功能、相关的信号调控机制,并且探讨影响occludin表达的因素,以期为occludin维持屏障功能完整提供理论支撑。Tight-junction(TJ)is a complex supramolecular entity composed of complete membrane proteins,membranes and soluble cytoplasmic proteins,which is distributed in almost all barrier structures in the body.It can maintain the polarity of epithelial cells,close the intercellular space and prevent the overflow of materials in the epithelial space,and is a highly dynamic signaling entity.Occludin is one of the most representative members of TJ proteins,mainly responsible for sealing intercellular connections,maintaining intercellular permeability,and participating in maintaining the integrity of vascular endothelium.The integrity of occludin is related to the integrity of TJ,and the function of occludin is often associated with the barrier properties of various tissues,and the abnormal expression of occludin is related to the occurrence and development of various diseases.Occludin contains abundant Ser and Thr residues and has multiple phosphorylation sites.Phosphorylation is necessary for the combination of occludin and TJ,which can regulate the location of occludin,regulate the expression of occludin,and enhance the permeability and barrier function of TJ.Therefore,phosphorylation regulation is a mechanism that cannot be ignored in the regulation of occludin function.Occludin also interacts with many other proteins,such as co-forming the cytoskeleton with ZO-1,and is regulated by a variety of transcription factors.Studies have confirmed that in pathological conditions,a variety of signaling pathways can disrupt the integrity of cell barrier by regulating the expression and distribution of occludin.Myosin light chain kinase(MLCK)signal transduction pathway is one of the important ways to regulate the structure and function of TJ.It influences the expression of occludin by altering the cytoskeleton.MLCK mainly uses the phosphorylation of myosin light chain(MLC)as a medium to promote actin contraction,secondary decomposition of tightly binding proteins,resulting in increased or changed cellular barrier permeability,and in
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