Nck1 and Grb2 localization patterns can distinguish invadopodia from podosomes.

Nck1 and Grb2 localization patterns can distinguish invadopodia from podosomes.
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Nck1 和 Grb2 定位模式可以区分侵袭足和足体。

DOI:
10.1016/j.ejcb.2010.08.006
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发表时间:
2011-02
影响因子:
6.6
通讯作者:
Condeelis, John
Condeelis, John
中科院分区:
生物学3区
文献类型:
--
作者:
Oser, Matthew;Dovas, Athanassios;Cox, Dianne;Condeelis, John

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侵袭足是在浸润性癌细胞中形成的降解基质的腹侧细胞表面结构。足体是在正常细胞类型中形成的基质降解结构,包括巨噬细胞、内皮细胞和平滑肌细胞,它们被认为在功能上与内陷畸形有关。介形虫和足体都富含调节肌动蛋白聚合的蛋白质,包括参与依赖N-黄蜂/黄蜂的Arp2/3-复合体激活的蛋白质。然而,目前还不清楚介体和足体是否使用不同的介体来激活依赖于N-黄蜂/黄蜂的Arp2/3-复合体。我们研究了转移性乳腺癌细胞、巨噬细胞中形成的足体以及转化成纤维细胞和PMA刺激的内皮细胞中形成的降解结构中N-WASP/WASP上游激活子NK1和Grb2的定位模式。我们提供的证据表明,NKK1特异性地定位于内侧足细胞,而不是形成于巨噬细胞中的足体或由Src转化的成纤维细胞和PMA刺激的内皮细胞形成的降解结构。相反,Grb2特异性地定位于在Src转化的成纤维细胞和PMA刺激的内皮细胞中形成的降解结构,而不是在巨噬细胞中形成的侵入体或足体。这些发现表明,不同的上游激活剂负责在卷足虫和足体中激活N-黄蜂/黄蜂,并且所有这些腹面细胞表面降解结构都具有不同的分子和结构特征。在我们的研究中发现的这些Nock1和Grb2的定位模式可以用来对腹侧细胞表面的降解性结构进行亚型分类。
Invadopodia are matrix-degrading ventral cell surface structures formed in invasive carcinoma cells. Podosomes are matrix-degrading structures formed in normal cell types including macrophages, endothelial cells, and smooth muscle cells that are believed to be related to invadopodia in function. Both invadopodia and podosomes are enriched in proteins that regulate actin polymerization including proteins involved in N-WASp/WASp-dependent Arp2/3-complex activation. However, it is unclear whether invadopodia and podosomes use distinct mediators for N-WASp/WASp-dependent Arp2/3-complex activation. We investigated the localization patterns of the upstream N-WASp/WASp activators Nck1 and Grb2 in invadopodia of metastatic mammary carcinoma cells, podosomes formed in macrophages, and degradative structures formed in Src-transformed fibroblasts and PMA-stimulated endothelial cells. We provide evidence that Nck1 specifically localizes to invadopodia, but not to podosomes formed in macrophages or degradative structures formed in Src-transformed fibroblasts and PMA-stimulated endothelial cells. In contrast, Grb2 specifically localizes to degradative structures formed in Src-transformed fibroblasts and PMA-stimulated endothelial cells, but not invadopodia or podosomes formed in macrophages. These findings suggest that distinct upstream activators are responsible for N-WASp/WASp activation in invadopodia and podosomes, and that all these ventral cell surface degradative structures have distinguishing molecular as well as structural characteristics. These patterns of Nck1 and Grb2 localization, identified in our study, can be used to sub classify ventral cell surface degradative structures.
DOI: 10.1242/jcs.051755
发表时间: 2009-11-01
影响因子: 4
作者:
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DOI: 10.1083/jcb.200708048
发表时间: 2008-03-10
期刊: The Journal of cell biology
影响因子: --
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发表时间: 2001-08-15
期刊: BLOOD
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