ARHGAP17 regulates the spatiotemporal activity of Cdc42 at invadopodia.
ARHGAP17 regulates the spatiotemporal activity of Cdc42 at invadopodia.
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ARHGAP17调节Cdc42在Invadopodia上的时空活性。
DOI：
10.1083/jcb.202207020
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发表时间：
2023-02-06
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影响因子：
--
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Kreider-Letterman et al. describe a novel mechanism for the regulation of Cdc42 dynamics at invadopodia by the Cdc42-GAP ARHGAP17, which targets to the invadopodia ring during assembly and relocates to the core to inactivate Cdc42 and initiate disassembly. Invadopodia formation is regulated by Rho GTPases. However, the molecular mechanisms that control Rho GTPase signaling at invadopodia remain poorly understood. Here, we have identified ARHGAP17, a Cdc42-specific RhoGAP, as a key regulator of invadopodia in breast cancer cells and characterized a novel ARHGAP17-mediated signaling pathway that controls the spatiotemporal activity of Cdc42 during invadopodia turnover. Our results show that during invadopodia assembly, ARHGAP17 localizes to the invadopodia ring and restricts the activity of Cdc42 to the invadopodia core, where it promotes invadopodia growth. Invadopodia disassembly starts when ARHGAP17 translocates from the invadopodia ring to the core, in a process that is mediated by its interaction with the Cdc42 effector CIP4. Once at the core, ARHGAP17 inactivates Cdc42 to promote invadopodia disassembly. Our results in invadopodia provide new insights into the coordinated transition between the activation and inactivation of Rho GTPases.
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影响因子：
8
作者：
Goicoechea, S. M.;Bednarski, B.;Garcia-Mata, R.;Prentice-Dunn, H.;Kim, H. J.;Otey, C. A.
通讯作者：
Otey, C. A.
影响因子：
8.4
作者：
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通讯作者：
El-Sibai, Mirvat
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：
3.5
作者：
Guo, Qisang;Xiong, Ying;Gao, Shujun
通讯作者：
Gao, Shujun
影响因子：
21.3
作者：
Chan Wah Hak L;Khan S;Di Meglio I;Law AL;Lucken-Ardjomande Häsler S;Quintaneiro LM;Ferreira APA;Krause M;McMahon HT;Boucrot E
通讯作者：
Boucrot E