Journal article
SH3BP1, an Exocyst-Associated RhoGAP, Inactivates Rac1 at the Front to Drive Cell Motility
Molecular cell, Vol.42(5), pp.650-661
06/10/2011
DOI: 10.1016/j.molcel.2011.03.032
PMCID: PMC3488376
PMID: 21658605
Abstract
The coordination of the several pathways involved in cell motility is poorly understood. Here, we identify SH3BP1, belonging to the RhoGAP family, as a partner of the exocyst complex and establish a physical and functional link between two motility-driving pathways, the Ral/exocyst and Rac signaling pathways. We show that SH3BP1 localizes together with the exocyst to the leading edge of motile cells and that SH3BP1 regulates cell migration via its GAP activity upon Rac1. SH3BP1 loss of function induces abnormally high Rac1 activity at the front, as visualized by in vivo biosensors, and disorganized and instable protrusions, as revealed by cell morphodynamics analysis. Consistently, constitutively active Rac1 mimics the phenotype of SH3BP1 depletion: slow migration and aberrant cell morphodynamics. Our finding that SH3BP1 downregulates Rac1 at the motile-cell front indicates that Rac1 inactivation in this location, as well as its activation by GEF proteins, is a fundamental requirement for cell motility.
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► The RhoGAP SH3BP1 interacts and colocalizes with the exocyst in motile cells ► SH3BP1 is required for cell migration because it inactivates Rac1-GTP at the front ► GDP/GTP cycling of Rac1 is needed to generate stable and organized protrusions ► SH3BP1 connects two motility-driving pathways: the Ral/exocyst and Rac pathways
Details
- Title: Subtitle
- SH3BP1, an Exocyst-Associated RhoGAP, Inactivates Rac1 at the Front to Drive Cell Motility
- Creators
- Maria Carla Parrini - Institut Curie, Centre de Recherche, Paris F-75248, FranceAmel Sadou-Dubourgnoux - Institut Curie, Centre de Recherche, Paris F-75248, FranceKazuhiro Aoki - Laboratory of Bioimaging and Cell Signaling, Graduate School of Biostudies, Kyoto University, Kyoto 606-8501, JapanKatsuyuki Kunida - Laboratory of Bioimaging and Cell Signaling, Graduate School of Biostudies, Kyoto University, Kyoto 606-8501, JapanMarco Biondini - Institut Curie, Centre de Recherche, Paris F-75248, FranceAnastassia Hatzoglou - Institut Curie, Centre de Recherche, Paris F-75248, FrancePatrick Poullet - Institut Curie, Centre de Recherche, Paris F-75248, FranceEtienne Formstecher - Hybrigenics Services SAS, Paris 75014, FranceCharles Yeaman - Department of Anatomy and Cell Biology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242-1109, USAMichiyuki Matsuda - Laboratory of Bioimaging and Cell Signaling, Graduate School of Biostudies, Kyoto University, Kyoto 606-8501, JapanCarine Rossé - Institut Curie, Centre de Recherche, Paris F-75248, FranceJacques Camonis - Institut Curie, Centre de Recherche, Paris F-75248, France
- Resource Type
- Journal article
- Publication Details
- Molecular cell, Vol.42(5), pp.650-661
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.molcel.2011.03.032
- PMID
- 21658605
- PMCID
- PMC3488376
- ISSN
- 1097-2765
- eISSN
- 1097-4164
- Language
- English
- Date published
- 06/10/2011
- Academic Unit
- Anatomy and Cell Biology; Internal Medicine
- Record Identifier
- 9984025311302771
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