Tks5 and SHIP2 regulate invadopodium maturation, but not initiation, in breast carcinoma cells.
Tks5 and SHIP2 regulate invadopodium maturation, but not initiation, in breast carcinoma cells.
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DOI：
10.1016/j.cub.2013.08.044
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发表时间：
2013-11-04
期刊：
影响因子：
9.2
通讯作者：
Condeelis, John
中科院分区：
文献类型：
--
作者：
Sharma, Ved P.;Eddy, Robert;Entenberg, David;Kai, Masayuki;Gertler, Frank B.;Condeelis, John
Tks 5调控内含子的形成，但在内含子的生命周期(起始、稳定、成熟)中发挥作用的确切时间尚不清楚。我们报告了基于高分辨率时空活细胞成像的新发现。Cortactin、N-WASP、Cofilin和肌动蛋白一起到达形成Intopodium前体，随后Tks 5招募。Tks 5不是前体启动所必需的，但对于前体稳定是必需的，这需要Tks 5的Phox同源(Px)结构域与PI(3，4)P2相互作用。在前驱体形成过程中，PI(3，4)P2均匀分布，但随后在核心启动后3-4min开始在前驱体核心聚集，反之，PI(3，4，5)P3在前驱体核心周围的环中聚集。SHIP2是一种5‘-肌醇磷酸酶，定位于内含子的核心，在内含子的局部调节PI(3，4)P2的水平。SHIP2到达异多糖前体的时间与PI(3，4)P2积累的开始时间一致。与SHIP2的迟到性一致，我们发现SHIP2的抑制并不影响前体的形成，但确实导致成熟的内陷和基质降解的减少，而SHIP2的过表达则增加了基质的降解。综上所述，这些发现导致我们提出了一个新的序贯模型，该模型为内陷前体的启动、稳定和成熟为功能性内陷提供了新的分子机制。
Tks5 regulates invadopodium formation, but the precise timing during invadopodium lifetime (initiation, stabilization, maturation) when Tks5 plays a role is not known. We report new findings based on high-resolution spatiotemporal live-cell imaging of invadopodium precursor assembly. Cortactin, N-WASP, cofilin, and actin arrive together to form the invadopodium precursor, followed by Tks5 recruitment. Tks5 is not required for precursor initiation but is needed for precursor stabilization, which requires the interaction of the phox homology (PX) domain of Tks5 with PI(3,4)P2. During precursor formation, PI(3,4)P2 is uniformly distributed but subsequently starts accumulating at the precursor core 3–4 min after core initiation, and conversely, PI(3,4,5)P3 gets enriched in a ring around the precursor core. SHIP2, a 5′-inositol phosphatase, localizes at the invadopodium core and regulates PI(3,4)P2 levels locally at the invadopodium. The timing of SHIP2 arrival at the invadopodium precursor coincides with the onset of PI(3,4)P2 accumulation. Consistent with its late arrival, we found that SHIP2 inhibition does not affect precursor formation but does cause decreases in mature invadopodia and matrix degradation, whereas SHIP2 overexpression increases matrix degradation. Together, these findings lead us to propose a new sequential model that provides novel insights into molecular mechanisms underlying invadopodium precursor initiation, stabilization, and maturation into a functional invadopodium.
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Nck1 和 Grb2 定位模式可以区分侵袭足和足体。
影响因子：
6.6
作者：
Oser, Matthew;Dovas, Athanassios;Cox, Dianne;Condeelis, John
通讯作者：
Condeelis, John
DOI：
10.1083/jcb.201103045
发表时间：
2011-11-28
期刊：
The Journal of cell biology
影响因子：
--
作者：
Magalhaes MA;Larson DR;Mader CC;Bravo-Cordero JJ;Gil-Henn H;Oser M;Chen X;Koleske AJ;Condeelis J
通讯作者：
Condeelis J
影响因子：
9.2
作者：
Bravo-Cordero, Jose Javier;Oser, Matthew;Chen, Xiaoming;Eddy, Robert;Hodgson, Louis;Condeelis, John
通讯作者：
Condeelis, John
影响因子：
3.3
作者：
Beaty BT;Sharma VP;Bravo-Cordero JJ;Simpson MA;Eddy RJ;Koleske AJ;Condeelis J
通讯作者：
Condeelis J
影响因子：
6.6
作者：
Blouw, Barbara;Seals, Darren F.;Courtneidge, Sara A.
通讯作者：
Courtneidge, Sara A.