Activation of the planar cell polarity formin DAAM1 leads to inhibition of endothelial cell proliferation, migration, and angiogenesis

Rong Ju; Pasquale Cirone; Shengda Lin; Hilary Griesbach; Diane C Slusarski; Craig M Crews

doi:10.1073/pnas.1001075107

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Activation of the planar cell polarity formin DAAM1 leads to inhibition of endothelial cell proliferation, migration, and angiogenesis

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Activation of the planar cell polarity formin DAAM1 leads to inhibition of endothelial cell proliferation, migration, and angiogenesis

Rong Ju, Pasquale Cirone, Shengda Lin, Hilary Griesbach, Diane C Slusarski and Craig M Crews

Proceedings of the National Academy of Sciences - PNAS, Vol.107(15), pp.6906-6911

04/13/2010

DOI: 10.1073/pnas.1001075107

PMCID: PMC2872452

PMID: 20351293

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Abstract

The Wnt/planar cell polarity (PCP) pathway regulates directed cell movement during development and was recently found to play a critical role in endothelial cell proliferation and angiogenesis [Zhang Y, et al. (2006) Chem Biol 13:1001–1009; Masckauchan TN, et al. (2006) Mol Biol Cell 17:5163–5172]. However, the mechanisms by which PCP signaling components regulate angiogenesis remain unknown. We report that expression of a constitutively active C-terminal domain of Dishevelled-associated activator of morphogenesis 1 (DAAM1) selectively inhibited endothelial cell proliferation. Moreover, this activated construct suppressed endothelial cell migration and the ability to form coordinated networks in vivo and in vitro. Although constitutively active DAAM1 (CDAAM1) induced both actin polymerization and microtubule (MT) stabilization, the stabilization of MTs alone was sufficient to inhibit endothelial cell growth selectively. Inhibition of actin polymerization alone by jasplakinolide treatment failed to reproduce the inhibitory effects of CDAAM1. These results indicate that DAAM1 regulates endothelial cell growth through MT stabilization in a cell type-selective manner and suggest that PCP signaling plays a pivotal role in angiogenesis by regulating MT stabilization.

Biological Sciences

HUVEC

Wnt signaling

zebrafish

dishevelled-associated activator of morphogenesis 1

microtubule stabilization

Details

Title: Subtitle: Activation of the planar cell polarity formin DAAM1 leads to inhibition of endothelial cell proliferation, migration, and angiogenesis
Creators: Rong Ju - Departments of
Pasquale Cirone - Departments of
Shengda Lin - Department of Biology
Hilary Griesbach - Department of Biology
Diane C Slusarski - Department of Biology
Craig M Crews - Departments of
Resource Type: Journal article
Publication Details: Proceedings of the National Academy of Sciences - PNAS, Vol.107(15), pp.6906-6911
DOI: 10.1073/pnas.1001075107
PMID: 20351293
PMCID: PMC2872452
NLM abbreviation: Proc Natl Acad Sci U S A
ISSN: 0027-8424
eISSN: 1091-6490
Publisher: National Academy of Sciences
Language: English
Date published: 04/13/2010
Academic Unit: Iowa Neuroscience Institute; Biology; Fraternal Order of Eagles Diabetes Research Center
Record Identifier: 9984070865502771

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