Evidence map›Paper›PMID 27486147›Full record

ArticleCirculation research2016

Rasip1-Mediated Rho GTPase Signaling Regulates Blood Vessel Tubulogenesis via Nonmuscle Myosin II.

David M Barry, Yeon Koo, Pieter R Norden, Lyndsay A Wylie, Ke Xu, Chonlarat Wichaidit, D Berfin Azizoglu, Yi Zheng, Melanie H Cobb, George E Davis and 1 more

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Article in Circulation research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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3 · Its place in the literature

Who cites it

46 citing papers in PubMed.

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  8. ARHGAP29 promotes keratinocyte proliferation and migration in vitro and is dispensable for in vivo wound healing.Developmental dynamics : an official publication of the American Association of Anatomists · 2025
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  13. EHMT2 promotes tumorigenesis inActa pharmaceutica Sinica. B · 2024
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

David M BarryFrom the Department of Molecular Biology and Center for Regenerative Science and Medicine (D.M.B., Y.K., K.X., D.B.A., O.C.) and Department of Pharmacology (C.W., M.H.C.), University of Texas Southwestern Medical Center, Dallas; Department of Medical Pharmacology and Physiology, University of Missouri, Columbia (P.R.N., G.E.D.); Department of Biology, University of North Carolina, Chapel Hill (L.A.W.); and Division of Experimental Hematology and Cancer Biology, Children's Hospital Research Foundation, University of Cincinnati, OH (Y.Z.).
Yeon KooFrom the Department of Molecular Biology and Center for Regenerative Science and Medicine (D.M.B., Y.K., K.X., D.B.A., O.C.) and Department of Pharmacology (C.W., M.H.C.), University of Texas Southwestern Medical Center, Dallas; Department of Medical Pharmacology and Physiology, University of Missouri, Columbia (P.R.N., G.E.D.); Department of Biology, University of North Carolina, Chapel Hill (L.A.W.); and Division of Experimental Hematology and Cancer Biology, Children's Hospital Research Foundation, University of Cincinnati, OH (Y.Z.).
Pieter R NordenFrom the Department of Molecular Biology and Center for Regenerative Science and Medicine (D.M.B., Y.K., K.X., D.B.A., O.C.) and Department of Pharmacology (C.W., M.H.C.), University of Texas Southwestern Medical Center, Dallas; Department of Medical Pharmacology and Physiology, University of Missouri, Columbia (P.R.N., G.E.D.); Department of Biology, University of North Carolina, Chapel Hill (L.A.W.); and Division of Experimental Hematology and Cancer Biology, Children's Hospital Research Foundation, University of Cincinnati, OH (Y.Z.).
Lyndsay A WylieFrom the Department of Molecular Biology and Center for Regenerative Science and Medicine (D.M.B., Y.K., K.X., D.B.A., O.C.) and Department of Pharmacology (C.W., M.H.C.), University of Texas Southwestern Medical Center, Dallas; Department of Medical Pharmacology and Physiology, University of Missouri, Columbia (P.R.N., G.E.D.); Department of Biology, University of North Carolina, Chapel Hill (L.A.W.); and Division of Experimental Hematology and Cancer Biology, Children's Hospital Research Foundation, University of Cincinnati, OH (Y.Z.).
Ke XuFrom the Department of Molecular Biology and Center for Regenerative Science and Medicine (D.M.B., Y.K., K.X., D.B.A., O.C.) and Department of Pharmacology (C.W., M.H.C.), University of Texas Southwestern Medical Center, Dallas; Department of Medical Pharmacology and Physiology, University of Missouri, Columbia (P.R.N., G.E.D.); Department of Biology, University of North Carolina, Chapel Hill (L.A.W.); and Division of Experimental Hematology and Cancer Biology, Children's Hospital Research Foundation, University of Cincinnati, OH (Y.Z.).
Chonlarat WichaiditFrom the Department of Molecular Biology and Center for Regenerative Science and Medicine (D.M.B., Y.K., K.X., D.B.A., O.C.) and Department of Pharmacology (C.W., M.H.C.), University of Texas Southwestern Medical Center, Dallas; Department of Medical Pharmacology and Physiology, University of Missouri, Columbia (P.R.N., G.E.D.); Department of Biology, University of North Carolina, Chapel Hill (L.A.W.); and Division of Experimental Hematology and Cancer Biology, Children's Hospital Research Foundation, University of Cincinnati, OH (Y.Z.).
D Berfin AzizogluFrom the Department of Molecular Biology and Center for Regenerative Science and Medicine (D.M.B., Y.K., K.X., D.B.A., O.C.) and Department of Pharmacology (C.W., M.H.C.), University of Texas Southwestern Medical Center, Dallas; Department of Medical Pharmacology and Physiology, University of Missouri, Columbia (P.R.N., G.E.D.); Department of Biology, University of North Carolina, Chapel Hill (L.A.W.); and Division of Experimental Hematology and Cancer Biology, Children's Hospital Research Foundation, University of Cincinnati, OH (Y.Z.).
Yi ZhengFrom the Department of Molecular Biology and Center for Regenerative Science and Medicine (D.M.B., Y.K., K.X., D.B.A., O.C.) and Department of Pharmacology (C.W., M.H.C.), University of Texas Southwestern Medical Center, Dallas; Department of Medical Pharmacology and Physiology, University of Missouri, Columbia (P.R.N., G.E.D.); Department of Biology, University of North Carolina, Chapel Hill (L.A.W.); and Division of Experimental Hematology and Cancer Biology, Children's Hospital Research Foundation, University of Cincinnati, OH (Y.Z.).
Melanie H CobbFrom the Department of Molecular Biology and Center for Regenerative Science and Medicine (D.M.B., Y.K., K.X., D.B.A., O.C.) and Department of Pharmacology (C.W., M.H.C.), University of Texas Southwestern Medical Center, Dallas; Department of Medical Pharmacology and Physiology, University of Missouri, Columbia (P.R.N., G.E.D.); Department of Biology, University of North Carolina, Chapel Hill (L.A.W.); and Division of Experimental Hematology and Cancer Biology, Children's Hospital Research Foundation, University of Cincinnati, OH (Y.Z.).
George E DavisFrom the Department of Molecular Biology and Center for Regenerative Science and Medicine (D.M.B., Y.K., K.X., D.B.A., O.C.) and Department of Pharmacology (C.W., M.H.C.), University of Texas Southwestern Medical Center, Dallas; Department of Medical Pharmacology and Physiology, University of Missouri, Columbia (P.R.N., G.E.D.); Department of Biology, University of North Carolina, Chapel Hill (L.A.W.); and Division of Experimental Hematology and Cancer Biology, Children's Hospital Research Foundation, University of Cincinnati, OH (Y.Z.).
Ondine CleaverFrom the Department of Molecular Biology and Center for Regenerative Science and Medicine (D.M.B., Y.K., K.X., D.B.A., O.C.) and Department of Pharmacology (C.W., M.H.C.), University of Texas Southwestern Medical Center, Dallas; Department of Medical Pharmacology and Physiology, University of Missouri, Columbia (P.R.N., G.E.D.); Department of Biology, University of North Carolina, Chapel Hill (L.A.W.); and Division of Experimental Hematology and Cancer Biology, Children's Hospital Research Foundation, University of Cincinnati, OH (Y.Z.). ondine.cleaver@utsouthwestern.edu.

Funding

UT Southwestern Medical Center Simmons Comprehensive Cancer CenterP30CA142543 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI MELANIE H. COBB · 2010 to 2026
$53.7M
Pre-doctoral Training Program in Integrative Vascular BiologyT32HL069768 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Christopher P. Mack · 2002 to 2026
$9.7M
Molecular regulation of Rho and Ras family GTPase activity controls vascular lumen formation.R01HL126518 · NHLBI · UT SOUTHWESTERN MEDICAL CENTER · PI CLEAVER, ONDINE B, DAVIS, GEORGE E · 2015 to 2023
$3.1M
Perfusable and beating engineered myocardium from human progenitor cells based onR01HL108670 · NHLBI · UNIVERSITY OF MINNESOTA · PI TRANQUILLO, ROBERT T · 2011 to 2014
$2.9M
Blood vessel tubulogenesis: Rasip1-directed GTPase signaling and cell polarity.R01HL113498 · NHLBI · UT SOUTHWESTERN MEDICAL CENTER · PI CLEAVER, ONDINE B · 2012 to 2015
$1.7M
Novel growth factor and signaling requirements for human capillary tube assemblyR01HL128584 · NHLBI · UNIVERSITY OF SOUTH FLORIDA · PI DAVIS, GEORGE E · 2015 to 2018
$1.5M
Endothelial Signals During OrganogenesisR01DK079862 · NIDDK · UT SOUTHWESTERN MEDICAL CENTER · PI CLEAVER, ONDINE B · 2007 to 2011
$1.5M
Hematopoietic stem cell cytokine control of developmental vascularizationR01HL105606 · NHLBI · UNIVERSITY OF MISSOURI-COLUMBIA · PI DAVIS, GEORGE E · 2011 to 2014
$1.5M
NCI NIH HHS P30 CA142543NHLBI NIH HHS R01 HL105606NHLBI NIH HHS R01 HL108670NHLBI NIH HHS R01 HL113498NHLBI NIH HHS R01 HL126518NHLBI NIH HHS R01 HL128584NHLBI NIH HHS T32 HL069768NIDDK NIH HHS R01 DK079862
6 · The paper itself

Abstract

rationaleVascular tubulogenesis is essential to cardiovascular development. Within initial vascular cords of endothelial cells, apical membranes are established and become cleared of cell-cell junctions, thereby allowing continuous central lumens to open. Rasip1 (Ras-interacting protein 1) is required for apical junction clearance, as well as for regulation of Rho GTPase (enzyme that hydrolyzes GTP) activity. However, it remains unknown how activities of different Rho GTPases are coordinated by Rasip1 to direct tubulogenesis.

objectiveThe aim of this study is to determine the mechanisms downstream of Rasip1 that drive vascular tubulogenesis. METHODS AND

resultsUsing conditional mouse mutant models and pharmacological approaches, we dissect GTPase pathways downstream of Rasip1. We show that clearance of endothelial cell apical junctions during vascular tubulogenesis depends on Rasip1, as well as the GTPase Cdc42 (cell division control protein 42 homolog) and the kinase Pak4 (serine/threonine-protein kinase 4). Genetic deletion of Rasip1 or Cdc42, or inhibition of Pak4, all blocks endothelial cell tubulogenesis. By contrast, inactivation of RhoA (Ras homologue gene family member A) signaling leads to vessel overexpansion, implicating actomyosin contractility in control of lumen diameter. Interestingly, blocking activity of NMII (nonmuscle myosin II) either before, or after, lumen morphogenesis results in dramatically different tubulogenesis phenotypes, suggesting time-dependent roles.

conclusionsRasip1 controls different pools of GTPases, which in turn regulate different pools of NMII to coordinate junction clearance (remodeling) and actomyosin contractility during vascular tubulogenesis. Rasip1 promotes activity of Cdc42 to activate Pak4, which in turn activates NMII, clearing apical junctions. Once lumens open, Rasip1 suppresses actomyosin contractility via inhibition of RhoA by Arhgap29, allowing controlled expansion of vessel lumens during embryonic growth. These findings elucidate the stepwise processes regulated by Rasip1 through downstream Rho GTPases and NMII.

Indexed as

AnimalsBlood VesselsCarrier ProteinsEmbryonic DevelopmentFemaleHumansHuman Umbilical Vein Endothelial CellsIntracellular Signaling Peptides and ProteinsMiceMyosin Type IIPregnancyrho GTP-Binding ProteinsSignal TransductionCarrier ProteinsIntracellular Signaling Peptides and ProteinsMyosin Type IIRasip1 protein, mouserho GTP-Binding Proteinsactin cytoskeletonendothelial cellsmorphogenesismyosin type IIRas homologue gene family member A GTP-binding proteinRas interacting protein 1tubulogenesis

Identifiers

PMID27486147
PMCPMC5026621

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