Dendritic cell podosomes are protrusive and invade the extracellular matrix using metalloproteinase MMP-14
Dendritic cell podosomes are protrusive and invade the extracellular matrix using metalloproteinase MMP-14
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DOI：
10.1242/jcs.056515
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发表时间：
2010-05-01
影响因子：
4
通讯作者：
Lucocq, John
中科院分区：
文献类型：
--
作者：
Gawden-Bone, Christian;Zhou, Zhongjun;Lucocq, John
足体是在单核细胞和造血细胞腹侧表面形成的富含肌动蛋白的点状结构。足体降解细胞外基质并被认为参与细胞迁移。一个关键问题是足体是否形成类似于癌细胞侵袭足的突起。我们使用电子显微镜结合传统和新型高分辨率结构照明光学显微镜来表征未成熟树突状细胞的足体。树突细胞足体由肌动蛋白灶组成，周围环绕着富含桩蛋白物质的特殊环形区域。我们发现足体是突出到浸渍有交联明胶的聚碳酸酯过滤器中的优先位点，在 24 小时内降解多达 2 毫米的基质。足小体相关的胶体金标记明胶基质的摄取似乎是通过大的吞噬体样结构或狭窄的管状内陷发生的。运动蛋白肌球蛋白-II 被排除在环或核心区域之外，但集中在它们周围，肌球蛋白-II 抑制剂布雷他汀 (Blebbistatin) 减少了足突的长度。最后，我们发现该系统中的降解、突出和内吞作用依赖于基质金属蛋白酶MMP-14。我们提出，足体通过肌球蛋白-II 依赖性突出与 MMP-14 依赖性降解和内吞作用相结合，介导树突状细胞在组织中的迁移。
Podosomes are spot-like actin-rich structures formed at the ventral surface of monocytic and haematopoietic cells. Podosomes degrade extracellular matrix and are proposed to be involved in cell migration. A key question is whether podosomes form protrusions similar to the invadopodia of cancer cells. We characterised podosomes of immature dendritic cells using electron microscopy combined with both conventional and novel high-resolution structured illumination light microscopy. Dendritic cell podosomes are composed of actin foci surrounded by a specialised ring region that is rich in material containing paxillin. We found that podosomes were preferential sites for protrusion into polycarbonate filters impregnated with crosslinked gelatin, degrading up to 2 mm of matrix in 24 hours. Podosome-associated uptake of colloidal gold-labelled gelatin matrix appeared to occur via large phagosome-like structures or narrow tubular invaginations. The motor protein myosin-II was excluded from ring or core regions but was concentrated around them and the myosin-II inhibitor Blebbistatin reduced the length of podosome protrusions. Finally, we found that degradation, protrusion and endocytosis in this system are dependent on the matrix metalloproteinase MMP-14. We propose that podosomes mediate migration of dendritic cells through tissues by means of myosin-II-dependent protrusion coupled to MMP-14-dependent degradation and endocytosis.