RCP-driven α5β1 recycling suppresses Rac and promotes RhoA activity via the RacGAP1–IQGAP1 complex

Jacquemet, Guillaume; Green, David M.; Bridgewater, Rebecca E.; Kriegsheim, Alex von; Humphries, Martin J.; Norman, Jim C.; Caswell, Patrick T.

doi:10.1083/jcb.201302041

Cited by 128 publications

(169 citation statements)

References 73 publications

(130 reference statements)

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“…As mentioned earlier, RCP also coordinates trafficking of a5b1 integrin and EGFR1 which leads to increased activation of the proinvasive PKB/Akt kinase downstream of EGFR1. Recently RacGAP1 was identified as Akt substrate in this pathway [76], which locally suppresses Rac activity while enhancing RhoA activity thereby promoting invasive migration into fibronectin-containing matrices [76]. The regulation of Akt signaling via the endosomal adaptor protein APPL1 illustrates the emerging importance of subcellular compartments as platforms for the coordination of migrationrelevant signaling cascades.…”

Section: Integrin Traffickingmentioning

confidence: 99%

On the move: endocytic trafficking in cell migration

Maritzen

Schachtner

Legler

2015

Cell. Mol. Life Sci.

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Directed cell migration is a fundamental process underlying diverse physiological and pathophysiological phenomena ranging from wound healing and induction of immune responses to cancer metastasis. Recent advances reveal that endocytic trafficking contributes to cell migration in multiple ways. (1) At the level of chemokines and chemokine receptors: internalization of chemokines by scavenger receptors is essential for shaping chemotactic gradients in tissue, whereas endocytosis of chemokine receptors and their subsequent recycling is key for maintaining a high responsiveness of migrating cells. (2) At the level of integrin trafficking and focal adhesion dynamics: endosomal pathways do not only modulate adhesion by delivering integrins to their site of action, but also by supplying factors for focal adhesion disassembly. (3) At the level of extracellular matrix reorganization: endosomal transport contributes to tumor cell migration not only by targeting integrins to invadosomes but also by delivering membrane type 1 matrix metalloprotease to the leading edge facilitating proteolysis-dependent chemotaxis. Consequently, numerous endocytic and endosomal factors have been shown to modulate cell migration. In fact key modulators of endocytic trafficking turn out to be also key regulators of cell migration. This review will highlight the recent progress in unraveling the contribution of cellular trafficking pathways to cell migration.

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Section: Integrin Traffickingmentioning

confidence: 99%

On the move: endocytic trafficking in cell migration

Maritzen

Schachtner

Legler

2015

Cell. Mol. Life Sci.

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“…Recent evidence clearly shows that, several integrin signals modulate the activity of Rho family GTPases through IQGAP1 (Wickstrom et al, 2010;Jacquemet et al, 2013aJacquemet et al, , 2013b, indicating IQGAP1 as a critical scaffold for signaling from transmembrane receptors.…”

Section: Control Of Iqgap Activitymentioning

confidence: 99%

IQGAPs as Key Regulators of Actin-cytoskeleton Dynamics

Watanabe

Wang

Kaibuchi

2015

Cell Struct. Funct.

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ABSTRACT. The actin-cytoskeleton plays a critical role in various biological processes, including cell migration, development, tissue remodeling, and memory formation. Both extracellular and intracellular signals regulate reorganization of the actin-cytoskeleton to modulate tissue architecture and cellular morphology in a spatiotemporal manner. Since the discovery that activation of Rho family GTPases induces actin-cytoskeleton reorganization, the mode of action of Rho family GTPases has been extensively studied and individual effectors have been characterized. The actin-binding protein IQGAP1 was identified as an effector of Rac and Cdc42 and is the founding member of the IQGAP family with two additional isoforms. The IQGAP family shows conserved domain organization, and each member displays a specific expression pattern in mammalian tissues. IQGAPs regulate the actin-cytoskeleton alone and with their binding partners, thereby controlling diverse cellular processes, such as cell migration and adhesion. Here, we introduce IQGAPs as an actin-cytoskeleton regulator.

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“…Because cell movement in ECM is a very complex process, we could not exclude the possibility that ARHGEF10 functions in non-Rab8-related invasive processes. Various studies have indicated that RhoA activation is necessary for invasive cell migration (Sakurai-Yageta et al, 2008;Friedl and Alexander, 2011;Jacquemet et al, 2013), suggesting that the RhoA GEF activity of ARHGEF10 might be involved in cell invasiveness. Future work will reveal the function of ARHGEF10 in cell invasion.…”

Section: Research Articlementioning

confidence: 99%

ARHGEF10 directs the localization of Rab8 to Rab6-positive executive vesicles

Shibata

Kawanai

Hara

et al. 2016

Journal of Cell Science

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The function of ARHGEF10, a known guanine nucleotide exchange factor (GEF) for RhoA with proposed roles in various diseases, is poorly understood. To understand the precise function of this protein, we raised a monoclonal antibody against ARHGEF10 and determined its localization in HeLa cells. ARHGEF10 was found to localize to vesicles containing Rab6 (of which there are three isoforms, Rab6a, Rab6b and Rab6c), Rab8 (of which there are two isoforms, Rab8a and Rab8b), and/or the secretion marker neuropeptide Y (NPY)-Venus in a Rab6-dependent manner. These vesicles were known to originate from the Golgi and contain secreted or membrane proteins. Ectopic expression of an N-terminal-truncated ARHGEF10 mutant led to the generation of large vesicle-like structures containing both Rab6 and Rab8. Additionally, small interfering (si)RNA-mediated knockdown of ARHGEF10 impaired the localization of Rab8 to these exocytotic vesicles. Furthermore, the invasiveness of MDA-MB231 cells was markedly decreased by knockdown of ARHGEF10, as well as of Rab8. From these results, we propose that ARHGEF10 acts in exocytosis and tumor invasion in a Rab8-dependent manner.

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RCP-driven α5β1 recycling suppresses Rac and promotes RhoA activity via the RacGAP1–IQGAP1 complex

Abstract: RCP-driven α5β1 recycling suppresses Rac activity through the RacGAP1–IQGAP1 complex to permit local activation of RhoA and drive invasive migration.

Cited by 128 publications

References 73 publications

On the move: endocytic trafficking in cell migration

On the move: endocytic trafficking in cell migration

IQGAPs as Key Regulators of Actin-cytoskeleton Dynamics

ARHGEF10 directs the localization of Rab8 to Rab6-positive executive vesicles

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