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Blood, 1 January 2009, Vol. 113, No. 1, pp. 244-253. Prepublished online as a Blood First Edition Paper on September 29, 2008; DOI 10.1182/blood-2008-04-153874. This Article Full Text Full Text (PDF) Supplemental Table and Figures All Versions of this Article: blood-2008-04-153874v1 113/1/244    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Ernkvist, M. Articles by Holmgren, L. Search for Related Content PubMed PubMed Citation Articles by Ernkvist, M. Articles by Holmgren, L. Related Collections Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  VASCULAR BIOLOGY The Amot/Patj/Syx signaling complex spatially controls RhoA GTPase activity in migrating endothelial cells Mira Ernkvist1, Nathalie Luna Persson1, Stéphane Audebert2, Patrick Lecine2, Indranil Sinha1, Miaoliang Liu3, Marc Schlueter4, Arie Horowitz3, Karin Aase1, Thomas Weide4, Jean-Paul Borg2, Arindam Majumdar5, and Lars Holmgren15 1 Department of Oncology and Pathology, Cancer Centrum Karolinska, Karolinska Institutet, Karolinska Hospital, Stockholm, Sweden; 2 Inserm, U599, Centre de Recherche en Cancérologie de Marseille, Department of Molecular Pharmacology, Marseille, France; Institut Paoli-Calmettes, Marseille, France; Université de la Méditerranée, Marseille, France; 3 Angiogenesis Research Center and Section of Cardiology, Department of Medicine, Dartmouth Medical School, Lebanon, NH; 4 University Hospital Muenster, Department of Internal Medicine D, Division of Molecular Nephrology, Muenster, Germany; and 5 Division of Matrix Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden Controlled regulation of Rho GTPase activity is an essential component mediating growth factor–stimulated migration. We have previously shown that angiomotin (Amot), a membrane-associated scaffold protein, plays a critical role during vascular patterning and endothelial migration during embryogenesis. However, the signaling pathways by which Amot controls directional migration are not known. Here we have used peptide pull-down and yeast 2-hybrid (Y2H) screening to identify proteins that interact with the C-terminal PDZ-binding motifs of Amot and its related proteins AmotL1 and 2. We report that Amot and its related proteins bind to the RhoA GTPase exchange factor (RhoGEF) protein Syx. We show that Amot forms a ternary complex together with Patj (or its paralogue Mupp1) and Syx. Using FRET analysis, we provide evidence that Amot controls targeting of RhoA activity to lamellipodia in vitro. We also report that, similar to Amot, morpholino knockdown of Syx in zebrafish results in inhibition of migration of intersegmental arteries. Taken together, our results indicate that the directional migration of capillaries in the embryo is governed by the Amot:Patj/Mupp1:Syx signaling that controls local GTPase activity. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: E. Roudier, N. Chapados, S. Decary, C. Gineste, C. Le Bel, J.-M. Lavoie, R. Bergeron, and O. Birot Angiomotin p80/p130 ratio: a new indicator of exercise-induced angiogenic activity in skeletal muscles from obese and non-obese rats? J. Physiol., August 15, 2009; 587(16): 4105 - 4119. [Abstract] [Full Text] [PDF] Y. Zheng, S. Vertuani, S. Nystrom, S. Audebert, I. Meijer, T. Tegnebratt, J.-P. Borg, P. Uhlen, A. Majumdar, and L. Holmgren Angiomotin-Like Protein 1 Controls Endothelial Polarity and Junction Stability During Sprouting Angiogenesis Circ. Res., July 31, 2009; 105(3): 260 - 270. [Abstract] [Full Text] [PDF] F. De Smet, I. Segura, K. De Bock, P. J. Hohensinner, and P. Carmeliet Mechanisms of Vessel Branching: Filopodia on Endothelial Tip Cells Lead the Way Arterioscler Thromb Vasc Biol, May 1, 2009; 29(5): 639 - 649. [Abstract] [Full Text] [PDF]

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