Integrin linked kinase (ILK) regulates podosome maturation and stability in dendritic cells.
Integrin linked kinase (ILK) regulates podosome maturation and stability in dendritic cells.
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DOI：
10.1016/j.biocel.2014.01.021
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发表时间：
2014-05
影响因子：
4
通讯作者：
Calle, Yolanda
中科院分区：
文献类型：
--
作者：
Griera, Mercedes;Martin-Villar, Ester;Banon-Rodriguez, Inmaculada;Blundell, Michael P.;Jones, Gareth E.;Anton, Ines M.;Thrasher, Adrian J.;Rodriguez-Puyol, Manuel;Calle, Yolanda
足突体是基于整合素的黏附体，对迁移树突状细胞（dc）的前导片的稳定和细胞外基质（ECM）的降解至关重要。我们之前的研究表明，可溶性因子和趋化因子如SDF - 1-a可触发dc中足小体的起始，而整合素配体则可促进dc中足小体的成熟和稳定。确切的细胞内信号通路，调节顺序组织的足质体成分响应于细胞外的线索仍然很大程度上不确定。Wiskott Aldrich综合征蛋白（WASP）介导肌动蛋白聚合和在纤丝肌动蛋白（F-actin）核心周围的圆形结构中整合素和相关蛋白的初始募集。我们现在已经确定了整合素连接激酶（ILK）周围的窝小体肌动蛋白核心。我们报告说，在足小体起始过程中，响应趋化因子的DC极化和肌动蛋白核心的组装需要pi3k依赖的维斯科特奥尔德里奇综合征蛋白（WASP）在点上独立于ILK聚集。ILK对于整合素和相关蛋白的聚集至关重要，从而导致足小体成熟和稳定，而足小体成熟和稳定是降解下层细胞外基质和树突状细胞跨越结缔组织屏障的侵袭性运动所必需的。我们得出结论，在新生足小体中，WASP调节dc极化以迁移和PI3K下游肌动蛋白聚合的启动。随后，ILK在足小体成熟和稳定过程中介导整合素相关蛋白的积累，从而在dc侵袭性迁移过程中有效降解下层ECM。
Podosomes are integrin-based adhesions fundamental for stabilisation of the leading lamellae in migrating dendritic cells (DCs) and for extracellular matrix (ECM) degradation. We have previously shown that soluble factors and chemokines such as SDF 1-a trigger podosome initiation whereas integrin ligands promote podosome maturation and stability in DCs. The exact intracellular signalling pathways that regulate the sequential organisation of podosomal components in response to extracellular cues remain largely undetermined. The Wiskott Aldrich Syndrome Protein (WASP) mediates actin polymerisation and the initial recruitment of integrins and associated proteins in a circular configuration surrounding the core of filamentous actin (F-actin) during podosome initiation. We have now identified integrin linked kinase (ILK) surrounding the podosomal actin core. We report that DC polarisation in response to chemokines and the assembly of actin cores during podosome initiation require PI3K-dependent clustering of the Wiskott Aldrich Syndrome Protein (WASP) in puncta independently of ILK. ILK is essential for the clustering of integrins and associated proteins leading to podosome maturation and stability that are required for degradation of the subjacent extracellular matrix and the invasive motility of DCs across connective tissue barriers. We conclude that WASP regulates DCs polarisation for migration and initiation of actin polymerisation downstream of PI3K in nascent podosomes. Subsequently, ILK mediates the accumulation of integrin-associated proteins during podosome maturation and stability for efficient degradation of the subjacent ECM during the invasive migration of DCs.
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DOI：
10.1038/nrm3141
发表时间：
2011-06-23
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
--
影响因子：
4
作者：
Stanchi, Fabio;Grashoff, Carsten;Van Obberghen-Schilling, Ellen
通讯作者：
Van Obberghen-Schilling, Ellen
影响因子：
4
作者：
Dovas, Athanassios;Gevrey, Jean-Claude;Cox, Dianne
通讯作者：
Cox, Dianne
影响因子：
4
作者：
Luxenburg, Chen;Winograd-Katz, Sabina;Geiger, Benjamin
通讯作者：
Geiger, Benjamin
影响因子：
2
作者：
Holt, M. R.;Calle, Y.;Dunn, G. A.
通讯作者：
Dunn, G. A.