A Rac/Cdc42 exchange factor complex promotes formation of lateral filopodia and blood vessel lumen morphogenesis.Citation formats

  • External authors:
  • Margherita Scarcia
  • Richard D Bagshaw
  • Kathryn McMahon
  • Gary Grant
  • Tracey Harvey
  • Maggie Yeo
  • Filomena O G Esteves
  • Helene H Thygesen
  • Pamela F Jones
  • Valerie Speirs
  • Andrew M Hanby
  • Peter J Selby
  • Mihaela Lorger
  • T Neil Dear
  • Tony Pawson
  • Christopher J Marshall
  • Georgia Mavria

Standard

A Rac/Cdc42 exchange factor complex promotes formation of lateral filopodia and blood vessel lumen morphogenesis. / Abraham, Sabu; Scarcia, Margherita; Bagshaw, Richard D; McMahon, Kathryn; Grant, Gary; Harvey, Tracey; Yeo, Maggie; Esteves, Filomena O G; Thygesen, Helene H; Jones, Pamela F; Speirs, Valerie; Hanby, Andrew M; Selby, Peter J; Lorger, Mihaela; Dear, T Neil; Pawson, Tony; Marshall, Christopher J; Mavria, Georgia.

In: Nature Communications, Vol. 6, 2015.

Research output: Contribution to journalArticle

Harvard

Abraham, S, Scarcia, M, Bagshaw, RD, McMahon, K, Grant, G, Harvey, T, Yeo, M, Esteves, FOG, Thygesen, HH, Jones, PF, Speirs, V, Hanby, AM, Selby, PJ, Lorger, M, Dear, TN, Pawson, T, Marshall, CJ & Mavria, G 2015, 'A Rac/Cdc42 exchange factor complex promotes formation of lateral filopodia and blood vessel lumen morphogenesis.', Nature Communications, vol. 6. https://doi.org/10.1038/ncomms8286

APA

Abraham, S., Scarcia, M., Bagshaw, R. D., McMahon, K., Grant, G., Harvey, T., ... Mavria, G. (2015). A Rac/Cdc42 exchange factor complex promotes formation of lateral filopodia and blood vessel lumen morphogenesis. Nature Communications, 6. https://doi.org/10.1038/ncomms8286

Vancouver

Author

Abraham, Sabu ; Scarcia, Margherita ; Bagshaw, Richard D ; McMahon, Kathryn ; Grant, Gary ; Harvey, Tracey ; Yeo, Maggie ; Esteves, Filomena O G ; Thygesen, Helene H ; Jones, Pamela F ; Speirs, Valerie ; Hanby, Andrew M ; Selby, Peter J ; Lorger, Mihaela ; Dear, T Neil ; Pawson, Tony ; Marshall, Christopher J ; Mavria, Georgia. / A Rac/Cdc42 exchange factor complex promotes formation of lateral filopodia and blood vessel lumen morphogenesis. In: Nature Communications. 2015 ; Vol. 6.

Bibtex

@article{76445d51ddd64605971a2b2101e43b86,
title = "A Rac/Cdc42 exchange factor complex promotes formation of lateral filopodia and blood vessel lumen morphogenesis.",
abstract = "During angiogenesis, Rho-GTPases influence endothelial cell migration and cell-cell adhesion; however it is not known whether they control formation of vessel lumens, which are essential for blood flow. Here, using an organotypic system that recapitulates distinct stages of VEGF-dependent angiogenesis, we show that lumen formation requires early cytoskeletal remodelling and lateral cell-cell contacts, mediated through the RAC1 guanine nucleotide exchange factor (GEF) DOCK4 (dedicator of cytokinesis 4). DOCK4 signalling is necessary for lateral filopodial protrusions and tubule remodelling prior to lumen formation, whereas proximal, tip filopodia persist in the absence of DOCK4. VEGF-dependent Rac activation via DOCK4 is necessary for CDC42 activation to signal filopodia formation and depends on the activation of RHOG through the RHOG GEF, SGEF. VEGF promotes interaction of DOCK4 with the CDC42 GEF DOCK9. These studies identify a novel Rho-family GTPase activation cascade for the formation of endothelial cell filopodial protrusions necessary for tubule remodelling, thereby influencing subsequent stages of lumen morphogenesis.",
author = "Sabu Abraham and Margherita Scarcia and Bagshaw, {Richard D} and Kathryn McMahon and Gary Grant and Tracey Harvey and Maggie Yeo and Esteves, {Filomena O G} and Thygesen, {Helene H} and Jones, {Pamela F} and Valerie Speirs and Hanby, {Andrew M} and Selby, {Peter J} and Mihaela Lorger and Dear, {T Neil} and Tony Pawson and Marshall, {Christopher J} and Georgia Mavria",
year = "2015",
doi = "10.1038/ncomms8286",
language = "English",
volume = "6",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Springer Nature",

}

RIS

TY - JOUR

T1 - A Rac/Cdc42 exchange factor complex promotes formation of lateral filopodia and blood vessel lumen morphogenesis.

AU - Abraham, Sabu

AU - Scarcia, Margherita

AU - Bagshaw, Richard D

AU - McMahon, Kathryn

AU - Grant, Gary

AU - Harvey, Tracey

AU - Yeo, Maggie

AU - Esteves, Filomena O G

AU - Thygesen, Helene H

AU - Jones, Pamela F

AU - Speirs, Valerie

AU - Hanby, Andrew M

AU - Selby, Peter J

AU - Lorger, Mihaela

AU - Dear, T Neil

AU - Pawson, Tony

AU - Marshall, Christopher J

AU - Mavria, Georgia

PY - 2015

Y1 - 2015

N2 - During angiogenesis, Rho-GTPases influence endothelial cell migration and cell-cell adhesion; however it is not known whether they control formation of vessel lumens, which are essential for blood flow. Here, using an organotypic system that recapitulates distinct stages of VEGF-dependent angiogenesis, we show that lumen formation requires early cytoskeletal remodelling and lateral cell-cell contacts, mediated through the RAC1 guanine nucleotide exchange factor (GEF) DOCK4 (dedicator of cytokinesis 4). DOCK4 signalling is necessary for lateral filopodial protrusions and tubule remodelling prior to lumen formation, whereas proximal, tip filopodia persist in the absence of DOCK4. VEGF-dependent Rac activation via DOCK4 is necessary for CDC42 activation to signal filopodia formation and depends on the activation of RHOG through the RHOG GEF, SGEF. VEGF promotes interaction of DOCK4 with the CDC42 GEF DOCK9. These studies identify a novel Rho-family GTPase activation cascade for the formation of endothelial cell filopodial protrusions necessary for tubule remodelling, thereby influencing subsequent stages of lumen morphogenesis.

AB - During angiogenesis, Rho-GTPases influence endothelial cell migration and cell-cell adhesion; however it is not known whether they control formation of vessel lumens, which are essential for blood flow. Here, using an organotypic system that recapitulates distinct stages of VEGF-dependent angiogenesis, we show that lumen formation requires early cytoskeletal remodelling and lateral cell-cell contacts, mediated through the RAC1 guanine nucleotide exchange factor (GEF) DOCK4 (dedicator of cytokinesis 4). DOCK4 signalling is necessary for lateral filopodial protrusions and tubule remodelling prior to lumen formation, whereas proximal, tip filopodia persist in the absence of DOCK4. VEGF-dependent Rac activation via DOCK4 is necessary for CDC42 activation to signal filopodia formation and depends on the activation of RHOG through the RHOG GEF, SGEF. VEGF promotes interaction of DOCK4 with the CDC42 GEF DOCK9. These studies identify a novel Rho-family GTPase activation cascade for the formation of endothelial cell filopodial protrusions necessary for tubule remodelling, thereby influencing subsequent stages of lumen morphogenesis.

U2 - 10.1038/ncomms8286

DO - 10.1038/ncomms8286

M3 - Article

VL - 6

JO - Nature Communications

T2 - Nature Communications

JF - Nature Communications

SN - 2041-1723

ER -