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The R-Ras/RIN2/Rab5 complex controls endothelial cell adhesion and morphogenesis via active integrin endocytosis and Rac signaling

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The R-Ras/RIN2/Rab5 complex controls endothelial cell adhesion and morphogenesis via active integrin endocytosis and Rac signaling. / Sandri, Chiara; Caccavari, Francesca; Valdembri, Donatella; Camillo, Chiara; Veltel, Stefan; Santambrogio, Martina; Lanzetti, Letizia; Bussolino, Federico; Ivaska, Johanna; Serini, Guido.

In: CELL RES, Vol. 22, No. 10, 01.10.2012, p. 1479-501.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Sandri, C, Caccavari, F, Valdembri, D, Camillo, C, Veltel, S, Santambrogio, M, Lanzetti, L, Bussolino, F, Ivaska, J & Serini, G 2012, 'The R-Ras/RIN2/Rab5 complex controls endothelial cell adhesion and morphogenesis via active integrin endocytosis and Rac signaling', CELL RES, vol. 22, no. 10, pp. 1479-501. https://doi.org/10.1038/cr.2012.110

APA

Sandri, C., Caccavari, F., Valdembri, D., Camillo, C., Veltel, S., Santambrogio, M., Lanzetti, L., Bussolino, F., Ivaska, J., & Serini, G. (2012). The R-Ras/RIN2/Rab5 complex controls endothelial cell adhesion and morphogenesis via active integrin endocytosis and Rac signaling. CELL RES, 22(10), 1479-501. https://doi.org/10.1038/cr.2012.110

Vancouver

Sandri C, Caccavari F, Valdembri D, Camillo C, Veltel S, Santambrogio M et al. The R-Ras/RIN2/Rab5 complex controls endothelial cell adhesion and morphogenesis via active integrin endocytosis and Rac signaling. CELL RES. 2012 Oct 1;22(10):1479-501. https://doi.org/10.1038/cr.2012.110

Bibtex

@article{ca1fe22a5a3548e18098f32f53311a66,
title = "The R-Ras/RIN2/Rab5 complex controls endothelial cell adhesion and morphogenesis via active integrin endocytosis and Rac signaling",
abstract = "During developmental and tumor angiogenesis, semaphorins regulate blood vessel navigation by signaling through plexin receptors that inhibit the R-Ras subfamily of small GTPases. R-Ras is mainly expressed in vascular cells, where it induces adhesion to the extracellular matrix (ECM) through unknown mechanisms. We identify the Ras and Rab5 interacting protein RIN2 as a key effector that in endothelial cells interacts with and mediates the pro-adhesive and -angiogenic activity of R-Ras. Both R-Ras-GTP and RIN2 localize at nascent ECM adhesion sites associated with lamellipodia. Upon binding, GTP-loaded R-Ras converts RIN2 from a Rab5 guanine nucleotide exchange factor (GEF) to an adaptor that first interacts at high affinity with Rab5-GTP to promote the selective endocytosis of ligand-bound/active β1 integrins and then causes the translocation of R-Ras to early endosomes. Here, the R-Ras/RIN2/Rab5 signaling module activates Rac1-dependent cell adhesion via TIAM1, a Rac GEF that localizes on early endosomes and is stimulated by the interaction with both Ras proteins and the vesicular lipid phosphatidylinositol 3-monophosphate. In conclusion, the ability of R-Ras-GTP to convert RIN2 from a GEF to an adaptor that preferentially binds Rab5-GTP allows the triggering of the endocytosis of ECM-bound/active β1 integrins and the ensuing funneling of R-Ras-GTP toward early endosomes to elicit the pro-adhesive and TIAM1-mediated activation of Rac1.",
keywords = "Antigens, CD29, Carrier Proteins, Cell Adhesion, Cells, Cultured, Endocytosis, Endosomes, Endothelial Cells, Extracellular Matrix, Guanine Nucleotide Exchange Factors, HeLa Cells, Humans, Phosphatidylinositol Phosphates, Protein Binding, RNA Interference, RNA, Small Interfering, Signal Transduction, rab5 GTP-Binding Proteins, rac GTP-Binding Proteins, ras Proteins",
author = "Chiara Sandri and Francesca Caccavari and Donatella Valdembri and Chiara Camillo and Stefan Veltel and Martina Santambrogio and Letizia Lanzetti and Federico Bussolino and Johanna Ivaska and Guido Serini",
year = "2012",
month = oct,
day = "1",
doi = "10.1038/cr.2012.110",
language = "English",
volume = "22",
pages = "1479--501",
journal = "CELL RES",
issn = "1001-0602",
publisher = "NATURE PUBLISHING GROUP",
number = "10",

}

RIS

TY - JOUR

T1 - The R-Ras/RIN2/Rab5 complex controls endothelial cell adhesion and morphogenesis via active integrin endocytosis and Rac signaling

AU - Sandri, Chiara

AU - Caccavari, Francesca

AU - Valdembri, Donatella

AU - Camillo, Chiara

AU - Veltel, Stefan

AU - Santambrogio, Martina

AU - Lanzetti, Letizia

AU - Bussolino, Federico

AU - Ivaska, Johanna

AU - Serini, Guido

PY - 2012/10/1

Y1 - 2012/10/1

N2 - During developmental and tumor angiogenesis, semaphorins regulate blood vessel navigation by signaling through plexin receptors that inhibit the R-Ras subfamily of small GTPases. R-Ras is mainly expressed in vascular cells, where it induces adhesion to the extracellular matrix (ECM) through unknown mechanisms. We identify the Ras and Rab5 interacting protein RIN2 as a key effector that in endothelial cells interacts with and mediates the pro-adhesive and -angiogenic activity of R-Ras. Both R-Ras-GTP and RIN2 localize at nascent ECM adhesion sites associated with lamellipodia. Upon binding, GTP-loaded R-Ras converts RIN2 from a Rab5 guanine nucleotide exchange factor (GEF) to an adaptor that first interacts at high affinity with Rab5-GTP to promote the selective endocytosis of ligand-bound/active β1 integrins and then causes the translocation of R-Ras to early endosomes. Here, the R-Ras/RIN2/Rab5 signaling module activates Rac1-dependent cell adhesion via TIAM1, a Rac GEF that localizes on early endosomes and is stimulated by the interaction with both Ras proteins and the vesicular lipid phosphatidylinositol 3-monophosphate. In conclusion, the ability of R-Ras-GTP to convert RIN2 from a GEF to an adaptor that preferentially binds Rab5-GTP allows the triggering of the endocytosis of ECM-bound/active β1 integrins and the ensuing funneling of R-Ras-GTP toward early endosomes to elicit the pro-adhesive and TIAM1-mediated activation of Rac1.

AB - During developmental and tumor angiogenesis, semaphorins regulate blood vessel navigation by signaling through plexin receptors that inhibit the R-Ras subfamily of small GTPases. R-Ras is mainly expressed in vascular cells, where it induces adhesion to the extracellular matrix (ECM) through unknown mechanisms. We identify the Ras and Rab5 interacting protein RIN2 as a key effector that in endothelial cells interacts with and mediates the pro-adhesive and -angiogenic activity of R-Ras. Both R-Ras-GTP and RIN2 localize at nascent ECM adhesion sites associated with lamellipodia. Upon binding, GTP-loaded R-Ras converts RIN2 from a Rab5 guanine nucleotide exchange factor (GEF) to an adaptor that first interacts at high affinity with Rab5-GTP to promote the selective endocytosis of ligand-bound/active β1 integrins and then causes the translocation of R-Ras to early endosomes. Here, the R-Ras/RIN2/Rab5 signaling module activates Rac1-dependent cell adhesion via TIAM1, a Rac GEF that localizes on early endosomes and is stimulated by the interaction with both Ras proteins and the vesicular lipid phosphatidylinositol 3-monophosphate. In conclusion, the ability of R-Ras-GTP to convert RIN2 from a GEF to an adaptor that preferentially binds Rab5-GTP allows the triggering of the endocytosis of ECM-bound/active β1 integrins and the ensuing funneling of R-Ras-GTP toward early endosomes to elicit the pro-adhesive and TIAM1-mediated activation of Rac1.

KW - Antigens, CD29

KW - Carrier Proteins

KW - Cell Adhesion

KW - Cells, Cultured

KW - Endocytosis

KW - Endosomes

KW - Endothelial Cells

KW - Extracellular Matrix

KW - Guanine Nucleotide Exchange Factors

KW - HeLa Cells

KW - Humans

KW - Phosphatidylinositol Phosphates

KW - Protein Binding

KW - RNA Interference

KW - RNA, Small Interfering

KW - Signal Transduction

KW - rab5 GTP-Binding Proteins

KW - rac GTP-Binding Proteins

KW - ras Proteins

U2 - 10.1038/cr.2012.110

DO - 10.1038/cr.2012.110

M3 - SCORING: Journal article

C2 - 22825554

VL - 22

SP - 1479

EP - 1501

JO - CELL RES

JF - CELL RES

SN - 1001-0602

IS - 10

ER -