Stadtmann Anika, Zarbock Alexander
Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Münster, Münster, Germany.
Curr Opin Hematol. 2017 Jan;24(1):38-45. doi: 10.1097/MOH.0000000000000294.
Since the discovery of the lack of kindlin-3 expression as the reason for the immunopathology leukocyte adhesion deficiency III syndrome, the role of kindlin-3 in inflammatory processes was investigated in a numerous studies. This review gives an overview about recent findings regarding the role of kindlin-3 in neutrophil activation and recruitment.
Kindlin-3, together with talin-1, contributes essentially to the activation of β2-integrins in neutrophils. During inside-out signaling, kindlin-3 binds to the β-cytoplasmic integrin tail and is indispensable for the integrin conformational shift into the high-affinity ligand binding conformation, but not for the intermediate (extended) conformation. During outside-in signaling (as a consequence of integrin ligand binding) kindlin-3 interacts with distinct signaling molecules and is required for cell-autonomous functions like migration and spreading.
Leukocyte adhesion deficiency III syndrome, which is caused by absence of kindlin-3, is a rarely occurring disease. However, the investigation of the clinical symptoms as well as the underlying molecular mechanisms gave rise to a huge amount of new insights into the processes of integrin activation in neutrophils and the consequences of defects in these processes.
自从发现缺乏kindlin-3表达是免疫病理学白细胞黏附缺陷III综合征的病因以来，众多研究对kindlin-3在炎症过程中的作用进行了探究。本综述概述了关于kindlin-3在中性粒细胞活化和募集中作用的最新研究结果。
Kindlin-3与踝蛋白-1一起，对中性粒细胞中β2整合素的活化起着至关重要的作用。在由内向外信号转导过程中，kindlin-3与整合素β亚基的胞质尾部结合，对于整合素构象转变为高亲和力配体结合构象是必不可少的，但对于中间（伸展）构象则并非如此。在由外向内信号转导过程中（由于整合素配体结合的结果），kindlin-3与不同的信号分子相互作用，并且是细胞自主功能（如迁移和铺展）所必需的。
由kindlin-3缺失引起的白细胞黏附缺陷III综合征是一种罕见疾病。然而，对其临床症状以及潜在分子机制的研究，为中性粒细胞中整合素活化过程以及这些过程缺陷的后果带来了大量新的见解。
