Kindlin-3及其生物学功能

Kindlin-3 and Its Biological Function

Kindlin-3属于Kindlin蛋白家族的一员,分布于造血细胞及内皮细胞。Kindlin家族成员高度同源,但具有不同的亚细胞定位及功能。Kindlin-3与踝蛋白(talin)通过其FERM结构域与整合素相互作用参与整合素的活化聚集,虽同含有FERM结构域,但两者作用位点并不相同,对整合素的影响亦有差异。活化的整合素参与多种细胞反应,介导细胞的黏附、伸展及迁移。之前的研究多集中在踝蛋白,但随着对Kindlin-3的深入研究,发现其作用或许并不亚于踝蛋白,但具体机制尚不明确。Kindlin-3缺失表现为严重出血、白细胞黏附缺陷,导致白细胞黏附缺陷综合征III。本文总结了Kindlin-3在血小板功能、炎症及免疫中的关键作用,还列举了其在多种疾病特别是恶性肿瘤中存在异常表达,且在不同肿瘤表达水平不同,并对肿瘤的生长、侵袭及转移产生影响,提示Kindlin-3除了与整合素结合之外,还可以通过其他机制发挥生物学功能。旨在对血栓与止血、炎症、免疫及肿瘤治疗提供新思路。

Kindlin-3,a member of the Kindlin protein family,is distributed in hematopoieticandendothelial cells.The members of the Kindlin family are highly homologous,but have different subcellular localization and functions.Kindlin-3 and talin participate in the activation and clustering of integrin through the interaction between their four-point-one,ezrin,radixin,moesin(FERM)domain and integrin.Although they both contain the FERM domain,their binding sites to integrin and effects on integrin are different.A variety of cell reactions are related to activated integrin,such as cell adhesion,extension and migration.Previous studies have mostly focused on talin.With the in-depth study of Kindlin-3,it is found that it also has many roles,but the specific mechanism is still unclear.Kindlin-3 deficiency leads tosevere bleeding and leukocyte adhesion defects(Leukocyte Adhesion Deficiency III).This paper summarizes the key role of Kindlin-3 in the platelet function,inflammation and immunity,and lists its abnormal expression in various diseases,especially in malignant tumors.We also coverits different expression levels in different tumors,which has an impact on tumor growth,invasion and metastasis,suggesting that Kindlin-3 may have more functions independent of integrin.We aim to provide new ideas for the treatment of thrombosis and hemostasis,inflammation,immunity and tumor.