School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore637551.
Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China518055.
J Cell Sci. 2021 Apr 15;134(8). doi: 10.1242/jcs.256115. Epub 2021 Apr 20.
Integrin-mediated cell-extracellular matrix (ECM) interactions play crucial roles in a broad range of physiological and pathological processes. Kindlins are important positive regulators of integrin activation. The FERM-domain-containing kindlin family comprises three members, kindlin-1, kindlin-2 and kindlin-3 (also known as FERMT1, FERMT2 and FERMT3), which share high sequence similarity (identity >50%), as well as domain organization, but exhibit diverse tissue-specific expression patterns and cellular functions. Given the significance of kindlins, analysis of their atomic structures has been an attractive field for decades. Recently, the structures of kindlin and its β-integrin-bound form have been obtained, which greatly advance our understanding of the molecular functions that involve kindlins. In particular, emerging evidence indicates that oligomerization of kindlins might affect their integrin binding and focal adhesion localization, positively or negatively. In this Review, we presented an update on the recent progress of obtaining kindlin structures, and discuss the implication for integrin activation based on kindlin oligomerization, as well as the possible regulation of this process.
整合素介导的细胞-细胞外基质（ECM）相互作用在广泛的生理和病理过程中发挥着关键作用。Kindlins 是整合素激活的重要正调控因子。FERM 结构域包含的 Kindlin 家族由三个成员组成，分别是 Kindlin-1、Kindlin-2 和 Kindlin-3（也称为 FERMT1、FERMT2 和 FERMT3），它们具有高度的序列相似性（同一性>50%）和结构域组织，但表现出不同的组织特异性表达模式和细胞功能。鉴于 Kindlins 的重要性，对其原子结构的分析几十年来一直是一个很有吸引力的领域。最近，Kindlin 及其与β整合素结合形式的结构已经被获得，这极大地促进了我们对涉及 Kindlins 的分子功能的理解。特别是，新出现的证据表明，Kindlins 的寡聚化可能会影响其整合素结合和焦点黏附定位，无论是积极的还是消极的。在这篇综述中，我们介绍了获得 Kindlin 结构的最新进展，并根据 Kindlin 寡聚化讨论了对整合素激活的影响，以及对这一过程的可能调节。
