Cortactin regulates cofilin and N-WASp activities to control the stages of invadopodium assembly and maturation.
Cortactin regulates cofilin and N-WASp activities to control the stages of invadopodium assembly and maturation.
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DOI：
10.1083/jcb.200812176
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发表时间：
2009-08-24
期刊：
影响因子：
--
通讯作者：
Condeelis J
中科院分区：
文献类型：
--
作者：
Oser M;Yamaguchi H;Mader CC;Bravo-Cordero JJ;Arias M;Chen X;Desmarais V;van Rheenen J;Koleske AJ;Condeelis J
侵袭伪足是侵袭性癌细胞中的基质降解膜突起。调节侵袭柄组装和成熟的机制尚不清楚。我们已经解剖了invadopodium组装和成熟的阶段，并表明invadopodia使用corneum磷酸化作为这些过程中的主开关。特别是，corneum磷酸化被发现调节cofilin和Arp 2/3复合物依赖的肌动蛋白聚合。Corneum直接结合cofilin并抑制其切断活性。皮质蛋白磷酸化需要释放这种抑制，因此cofilin可以切断肌动蛋白丝，在侵入伪足处产生倒刺末端，以支持Arp 2/3依赖的肌动蛋白聚合。在倒刺末端形成后，corpine被去磷酸化，其阻断cofilin切断活性，从而稳定侵入伪足。这些发现确定了转移性癌细胞侵袭伪足中肌动蛋白聚合的新机制，并定义了侵袭伪足组装和成熟的四个不同阶段，包括侵袭伪足前体形成、肌动蛋白聚合、稳定和基质降解。
Invadopodia are matrix-degrading membrane protrusions in invasive carcinoma cells. The mechanisms regulating invadopodium assembly and maturation are not understood. We have dissected the stages of invadopodium assembly and maturation and show that invadopodia use cortactin phosphorylation as a master switch during these processes. In particular, cortactin phosphorylation was found to regulate cofilin and Arp2/3 complex–dependent actin polymerization. Cortactin directly binds cofilin and inhibits its severing activity. Cortactin phosphorylation is required to release this inhibition so cofilin can sever actin filaments to create barbed ends at invadopodia to support Arp2/3-dependent actin polymerization. After barbed end formation, cortactin is dephosphorylated, which blocks cofilin severing activity thereby stabilizing invadopodia. These findings identify novel mechanisms for actin polymerization in the invadopodia of metastatic carcinoma cells and define four distinct stages of invadopodium assembly and maturation consisting of invadopodium precursor formation, actin polymerization, stabilization, and matrix degradation.
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影响因子：
11.4
作者：
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通讯作者：
Condeelis, John