ARHGAP17 regulates the spatiotemporal activity of Cdc42 at invadopodia.

Abstract

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.

• Authors: Gabriel Kreider-Letterman, Abel Castillo, Eike K Mahlandt, Joachim Goedhart, Agustin Rabino, Silvia Goicoechea, Rafael Garcia-Mata
• Journal: The Journal of cell biology (J Cell Biol) Vol. 222 Issue 2 (02 06 2023) ISSN: 1540-8140 [Electronic] United States
• PMID: 36571786 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2022 Kreider-Letterman et al.

Chemical References

• cdc42 GTP-Binding Protein
• rho GTP-Binding Proteins
• ARHGAP17 protein, human
• GTPase-Activating Proteins
• CDC42 protein, human

Topics

• cdc42 GTP-Binding Protein (genetics, metabolism)
• Podosomes (metabolism)
• rho GTP-Binding Proteins (genetics, metabolism)
• Signal Transduction
• Cell Line, Tumor
• Humans
• Breast Neoplasms
• GTPase-Activating Proteins (metabolism)