Macrophage Migration and Phagocytosis Are Controlled by Kindlin-3's Link to the Cytoskeleton.
Macrophage Migration and Phagocytosis Are Controlled by Kindlin-3's Link to the Cytoskeleton.
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DOI：
10.4049/jimmunol.1901134
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发表时间：
2020-04-01
期刊：
影响因子：
--
通讯作者：
Byzova TV
中科院分区：
文献类型：
--
作者：
Liu H;Zhu L;Dudiki T;Gabanic B;Good L;Podrez EA;Cherepanova OA;Qin J;Byzova TV
从黏附到迁移和吞噬的主要髓系细胞功能是由整合素黏附复合体(也称为黏附复合体)介导的。直接整合素结合伙伴Kindlin-3的存在对这些功能至关重要，它的缺乏会导致人类严重的免疫缺陷。然而，Kindlin-3是如何被整合到粘附物中的，以及它的功能是如何被调控的，人们对此知之甚少。在这里，我们用核磁共振技术证明了Kindlin-3在其F0结构域内通过G43/L47直接与PXN(Paxlin)和LPXN(Leupasin)相互作用。令人惊讶的是，Kindlin-3-Pxn/LPxn在Raw 264.7巨噬细胞中的相互作用被破坏，促进了细胞的扩散和极化，导致了一般细胞运动性和定向细胞迁移的上调，这与Kindlin-3基因敲除的后果形成了鲜明的对比。此外，Kindlin-3-PXN/LPXN结合的破坏促进了间充质运动向阿米巴运动模式的转变以及吞噬功能的增强。因此，Kindlin-3和关键的黏附成员PXN/LPXN之间的这些新的联系限制了髓系细胞的运动和吞噬，从而提供了一个重要的免疫调节机制。
Major myeloid cell functions from adhesion to migration and phagocytosis are mediated by integrin adhesion complexes, also known as adhesome. The presence of a direct integrin binding partner Kindlin-3 is crucial for these functions and its lack causes severe immunodeficiency in humans. However, how Kindlin-3 is incorporated into the adhesome, and how its function is regulated, is poorly understood. Here, using NMR we show that Kindlin-3 directly interacts with PXN (Paxillin) and LPXN (Leupaxin) via G43/L47 within its F0 domain. Surprisingly, disruption of Kindlin-3-PXN/LPXN interactions in Raw 264.7 macrophages promoted cell spreading and polarization, resulting in upregulation of both, general cell motility and directed cell migration, which is in a drastic contrast to the consequences of Kindlin-3 knockout. Moreover, disruption of Kindlin-3-PXN/LPXN binding promoted the transition from mesenchymal to amoeboid mode of movement as well as augmented phagocytosis. Thus, these novel links between Kindlin-3 and key adhesome members, PXN/LPXN limit myeloid cell motility and phagocytosis, thereby providing an important immune regulatory mechanism.
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影响因子：
19
作者：
Diz-Muñoz A;Fletcher DA;Weiner OD
通讯作者：
Weiner OD
DOI：
10.1083/jcb.201701176
发表时间：
2017-11-06
期刊：
The Journal of cell biology
影响因子：
--
作者：
Böttcher RT;Veelders M;Rombaut P;Faix J;Theodosiou M;Stradal TE;Rottner K;Zent R;Herzog F;Fässler R
通讯作者：
Fässler R
DOI：
10.1073/pnas.1207968109
发表时间：
2012-09-04
影响因子：
11.1
作者：
Bergert, Martin;Chandradoss, Stanley D.;Paluch, Ewa
通讯作者：
Paluch, Ewa
影响因子：
64.5
作者：
Liu J;Lichtenberg T;Hoadley KA;Poisson LM;Lazar AJ;Cherniack AD;Kovatich AJ;Benz CC;Levine DA;Lee AV;Omberg L;Wolf DM;Shriver CD;Thorsson V;Cancer Genome Atlas Research Network;Hu H
通讯作者：
Hu H
影响因子：
21.1
作者：
Liu, Yan;Zhu, Yun;Zhang, Rongguang
通讯作者：
Zhang, Rongguang