Imperial College London

ProfessorVaniaBraga

Faculty of MedicineNational Heart & Lung Institute

Professor of Cellular Signalling
 
 
 
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Contact

 

+44 (0)20 7594 3233v.braga

 
 
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Location

 

Office no. 105Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Publication Type
Year
to

84 results found

Tzircotis G, Braga VMM, Caron E, 2011, RhoG is required for both Fc gamma R- and CR3-mediated phagocytosis, JOURNAL OF CELL SCIENCE, Vol: 124, Pages: 2897-2902, ISSN: 0021-9533

Phagocytosis is a highly ordered process orchestrated by signalling through Rho GTPases to locally organise the actin cytoskeleton and drive particle uptake. Specific Rho family members that regulate phagocytosis are not known, as the majority of studies have relied on the use of dominant-negative mutants and/or toxins, which can inactivate multiple Rho GTPases. To identify the relevant GTPases for phagocytosis through the Fcγ receptor (FcγR) and complement receptor 3 (CR3), we depleted 20 Rho proteins individually in an RNA interference (RNAi) screen. We find that distinct GTPase subsets are required for actin polymerisation and uptake by macrophages: FcγR-dependent engulfment requires Cdc42 and Rac2 (but not Rac1), whereas CR3 requires RhoA. Surprisingly, RhoG is required for particle uptake through both FcγR and CR3. RhoG has been previously linked to Rac and Cdc42 signalling in different model systems, but not to RhoA. Interestingly, we find that RhoG is also recruited and activated at phagocytic cups downstream of FcγR and CR3, irrespective of their distinct actin structures and mechanisms of internalisation. Thus, the functional links between RhoG and RhoA downstream of CR3-dependent phagocytosis are new and unexpected. Our data suggest a broad role for RhoG in consolidating signals from multiple receptors during phagocytosis.

Journal article

Keraudren K, Spitaler M, Braga VMM, Rueckert D, Pizarro Let al., 2011, Two-step watershed segmentation of epithelial cells., Heidelberg, Germany, 6th International Workshop on Microscopic Image Analysis with Applications in Biology.

Conference paper

Frasa MAM, Maximiano FC, Smolarczyk K, Francis RE, Betson ME, Lozano E, Goldenring J, Seabra MC, Rak A, Ahmadian MR, Braga VMMet al., 2010, Armus Is a Rac1 Effector that Inactivates Rab7 and Regulates E-Cadherin Degradation, CURRENT BIOLOGY, Vol: 20, Pages: 198-208, ISSN: 0960-9822

Journal article

Erasmus J, Aresta S, Nola S, Caron E, Braga VMMet al., 2010, Newly formed E-cadherin contacts do not activate Cdc42 or induce filopodia protrusion in human keratinocytes, BIOLOGY OF THE CELL, Vol: 102, Pages: 13-24, ISSN: 0248-4900

Journal article

Liebig T, Erasmus J, Kalaji R, Davies D, Loirand G, Ridley A, Braga VMMet al., 2009, RhoE Is Required for Keratinocyte Differentiation and Stratification, MOLECULAR BIOLOGY OF THE CELL, Vol: 20, Pages: 452-463, ISSN: 1059-1524

Journal article

Lozano E, Frasa MAM, Smolarczyk K, Knaus UG, Braga VMMet al., 2008, PAK is required for the disruption of E-cadherin adhesion by the small GTPase Rac, JOURNAL OF CELL SCIENCE, Vol: 121, Pages: 933-938, ISSN: 0021-9533

Journal article

Fujita Y, Hogan C, Braga, V M Met al., 2006, Regulation of cell-cell adhesion by Rap1, Methods in Enzymology, Editors: Der, Publisher: Elsevier, Pages: 359-372

Book chapter

Braga VM, 2006, Methods in Enzymology, Methods in Enzymology

Book chapter

Erasmus J, Braga VMM, 2006, Rho GTPase activation by cell-cell adhesion, Methods in Enzymology, Editors: Der, Hall, Publisher: Elsevier, Pages: 402-415

Book chapter

Zhang JK, Betson M, Erasmus J, Zeikos K, Bailly M, Cramer LP, Braga VMMet al., 2005, Actin at cell-cell junctions is composed of two dynamic and functional populations, JOURNAL OF CELL SCIENCE, Vol: 118, Pages: 5549-5562, ISSN: 0021-9533

Journal article

Braga VMM, Yap AS, 2005, The challenges of abundance: epithelial junctions and small GTPase signalling, CURRENT OPINION IN CELL BIOLOGY, Vol: 17, Pages: 466-474, ISSN: 0955-0674

Journal article

Pratt SJ, Epple H, Ward M, Feng YF, Braga VM, Longmore GDet al., 2005, The LIM protein Ajuba influences p130Cas localization and Rac1 activity during cell migration, JOURNAL OF CELL BIOLOGY, Vol: 168, Pages: 813-824, ISSN: 0021-9525

Cell migration requires extension of lamellipodia that are stabilized by formation of adhesive complexes at the leading edge. Both processes are regulated by signaling proteins recruited to nascent adhesive sites that lead to activation of Rho GTPases. The Ajuba/Zyxin family of LIM proteins are components of cellular adhesive complexes. We show that cells from Ajuba null mice are inhibited in their migration, without associated abnormality in adhesion to extracellular matrix proteins, cell spreading, or integrin activation. Lamellipodia production, or function, is defective and there is a selective reduction in the level and tyrosine phosphorylation of FAK, p130Cas, Crk, and Dock180 at nascent focal complexes. In response to migratory cues Rac activation is blunted in Ajuba null cells, as detected biochemically and by FRET analysis. Ajuba associates with the focal adhesion-targeting domain of p130Cas, and rescue experiments suggest that Ajuba acts upstream of p130Cas to localize p130Cas to nascent adhesive sites in migrating cells thereby leading to the activation of Rac.

Journal article

Fujita Y, Braga VMM, 2005, Epithelial cell shape and Rho small GTPases., Singapore, Signalling Networks in Cell Shape and Motility, Publisher: Novartis Foundation Symposium, Pages: 144-158

Conference paper

Braga VMM, Balda MS, 2004, Regulation of cell-cell adhesion, SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY, Vol: 15, Pages: 631-632, ISSN: 1084-9521

Journal article

Braga V, 2004, Rho GTPases and cell-cell adhesion, GBM Annual Fall meeting M�nster 2004, Vol: 2004

Journal article

Hogan C, Serpente N, Cogram P, Hosking CR, Bialucha CU, Feller SM, Braga VMM, Birchmeier W, Fujita Yet al., 2004, Rap1 regulates the formation of E-cadherin-based cell-cell contacts, MOLECULAR AND CELLULAR BIOLOGY, Vol: 24, Pages: 6690-6700, ISSN: 0270-7306

Journal article

Braga VMM, Balda M, 2004, Regulation of Cell Adhesion - Seminars in Cell and Developmental Biology, Publisher: Elsevier

Book

Lozano E, Betson M, Braga VMM, 2003, Tumor progression: small GTPases and loss of cell-cell adhesion, BIOESSAYS, Vol: 25, Pages: 452-463, ISSN: 0265-9247

Journal article

Harwood A, Braga VMM, 2003, Cdc42 & GSK-3: signals at the crossroads, NATURE CELL BIOLOGY, Vol: 5, Pages: 275-277, ISSN: 1465-7392

Journal article

Marie H, Pratt SJ, Betson M, Epple H, Kittler JT, Meek L, Moss SJ, Troyanovsky S, Attwell D, Longmore GD, Braga VMMet al., 2003, The LIM protein Ajuba is recruited to cadherin-dependent cell junctions through an association with α-catenin, JOURNAL OF BIOLOGICAL CHEMISTRY, Vol: 278, Pages: 1220-1228, ISSN: 0021-9258

Journal article

Braga V, Betson ME, 2003, Cell-cell adhesion., Rho GTPses, Editors: Symons, Publisher: Landes Bioscience and Eurekah.com

Book chapter

Betson M, Lozano E, Zhang J, Braga VMMet al., 2002, Rac activation upon cell-cell contact formation is dependent on signaling from the epidermal growth factor receptor., J Biol Chem, Vol: 277, Pages: 36962-36969, ISSN: 0021-9258

Cadherins are transmembrane receptors that mediate cell-cell adhesion. They play an essential role in embryonic development and maintenance of tissue architecture. The Rho family small GTPases regulate actin cytoskeletal dynamics in different cell types. The function of two family members, Rho and Rac, is required for the stability of cadherins at cell-cell contacts. Consistent with the published data we have found that Rac is activated upon induction of intercellular adhesion in epithelial cells. This activation is dependent on functional cadherins (Nakagawa, M., Fukata, M., Yamaga, M., Itoh, N., and Kaibuchi, K. (2001) J. Cell Sci. 114, 1829-1838; Noren, N. K., Niessen, C. M., Gumbiner, B. M., and Burridge, K. (2001) J. Biol. Chem. 276, 3305-3308). Here we show for the first time that clustering of cadherins using antibody-coated beads is sufficient to promote Rac activation. In the presence of Latrunculin B, Rac can be partially activated by antibody-clustered cadherins. These results suggest that actin polymerization is not required for initial Rac activation. Contrary to what has been described before, phosphatidylinositol 3-kinases are not involved in Rac activation following cell-cell adhesion in keratinocytes. Interestingly, inhibition of epidermal growth factor receptor signaling efficiently blocks the increased Rac-GTP levels observed after contact formation. We conclude that cadherin-dependent adhesion can activate Rac via epidermal growth factor receptor signaling.

Journal article

Braga VMM, 2002, Cell-cell adhesion and signalling, CURRENT OPINION IN CELL BIOLOGY, Vol: 14, Pages: 546-556, ISSN: 0955-0674

Journal article

Braga VMM, 2002, GEF without a Dbl domain?, NATURE CELL BIOLOGY, Vol: 4, Pages: E188-E190, ISSN: 1465-7392

Journal article

Lampugnani MG, Zanetti A, Breviario F, Balconi G, Orsenigo F, Corada M, Spagnuolo R, Betson M, Braga V, Dejana Eet al., 2002, VE-cadherin regulates endothelial actin activating Rac and increasing membrane association of Tiam, MOLECULAR BIOLOGY OF THE CELL, Vol: 13, Pages: 1175-1189, ISSN: 1059-1524

Journal article

Braga V, Harwood AJ, 2001, 'Super glue', NATURE CELL BIOLOGY, Vol: 3, Pages: E168-E170, ISSN: 1465-7392

Journal article

Braga V, 2001, Cadherin adhesion regulation in keratinocytes, Pages: 1-36, ISBN: 9780199638642

Book chapter

Braga V, 2000, Epithelial cell shape: cadherins and small GTPases., Exp Cell Res, Vol: 261, Pages: 83-90, ISSN: 0014-4827

Cadherins are cell-cell adhesion receptors that are essential for the establishment of the epithelial cell shape and maintenance of the differentiated epithelial phenotype. In order to show efficient adhesion, cadherin receptors require an association with actin filaments and the activity of RHO proteins. The RHO family of small GTPases is primarily involved in the reorganization of the cytoskeleton. In different cell types, each member of the family can induce specific types of organization of actin filaments: stress fibers (Rho), lamellae/ruffles (Rac), or filopodia (Cdc42). This review focuses on how the function of small GTPases may impinge on the regulation of cadherin-dependent adhesion. In particular, it discusses the impact that the above cytoskeletal structures induced by RHO proteins have on the development of epithelial morphology. Finally, the participation of small GTPase-interacting proteins is considered during the remodeling of cell shape that follows cell-cell contact formation.

Journal article

Braga VMM, Betson M, Li XD, Lamarche-Vane Net al., 2000, Activation of the small GTPase Rac is sufficient to disrupt cadherin-dependent cell-cell adhesion in normal human keratinocytes, MOLECULAR BIOLOGY OF THE CELL, Vol: 11, Pages: 3703-3721, ISSN: 1059-1524

Journal article

Braga VM, Betson M, Li X, Lamarche-Vane Net al., 2000, Activation of the small GTPase Rac is sufficient to disrupt cadherin-dependent cell-cell adhesion in normal human keratinocytes., Mol Biol Cell, Vol: 11, Pages: 3703-3721, ISSN: 1059-1524

To achieve strong adhesion to their neighbors and sustain stress and tension, epithelial cells develop many different specialized adhesive structures. Breakdown of these structures occurs during tumor progression, with the development of a fibroblastic morphology characteristic of metastatic cells. During Ras transformation, Rac-signaling pathways participate in the disruption of cadherin-dependent adhesion. We show that sustained Rac activation per se is sufficient to disassemble cadherin-mediated contacts in keratinocytes, in a concentration- and time-dependent manner. Cadherin receptors are removed from junctions before integrin receptors, suggesting that pathways activated by Rac can specifically interfere with cadherin function. We mapped an important region for disruption of junctions to the putative second effector domain of the Rac protein. Interestingly, although this region overlaps the domain necessary to induce lamellipodia, we demonstrate that the disassembly of cadherin complexes is a new Rac activity, distinct from Rac-dependent lamellipodia formation. Because Rac activity is also necessary for migration, Rac is a good candidate to coordinately regulate cell-cell and cell-substratum adhesion during tumorigenesis.

Journal article

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