Neuropilin-1 regulates a new VEGF-induced gene, Phactr-1, which controls tubulogenesis and modulates lamellipodial dynamics in human endothelial cells

被引：66

作者：

Allain, Barbara ^{[1
,2
]}

Jarray, Rafika ^{[1
]}

Borriello, Lucia ^{[1
,2
]}

Leforban, Bertrand ^{[2
]}

Dufour, Sylvie ^{[3
]}

Liu, Wang-qing ^{[1
]}

Pamonsinlapatham, Perayot ^{[4
]}

Bianco, Sara ^{[1
]}

Larghero, Jerome ^{[5
,6
]}

Hadj-Slimane, Reda ^{[2
]}

Garbay, Christiane ^{[1
]}

Raynaud, Francoise ^{[1
]}

Lepelletier, Yves ^{[7
]}

机构：

[1] Univ Paris 05, Lab Chim & Biochim Pharmacol & Toxicol, UMR CNRS 8601, F-75006 Paris, France

[2] Tragex Pharma, F-75015 Paris, France

[3] UMR 144 CNRS Inst Curie, F-75005 Paris, France

[4] Silpakorn Univ, Fac Pharm, Nakhon Pathom 73000, Thailand

[5] Univ Paris 05, Hop St Louis, Unite Therapie Cellulaire, Paris, France

[6] Hop St Louis, Inst Univ Hematol, INSERM UMR940, Paris, France

[7] Univ Paris 05, F-91200 Athis Mons, France

来源：

CELLULAR SIGNALLING | 2012年 / 24卷 / 01期

关键词：

Phactr-1; Neuropilin-1; Actin polymerization; Lamellipodia; PP1; Tubulogenesis; PROTEIN PHOSPHATASE 1; GROWTH-FACTOR; ACTIN CYTOSKELETON; BINDING; ANGIOGENESIS; PROTEIN-PHOSPHATASE-1; SCAPININ; MOTILITY; NEURABIN; DOMAINS;

D O I：

10.1016/j.cellsig.2011.09.003

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Recently, we identified a new Vascular Endothelial Growth Factor (VEGF)-A(165)-induced gene Phactr-1, (Phosphatase Actin Regulator-1). We reported that Phactr-1 gene silencing inhibited tube formation in human umbilical endothelial cells (HUVECs) indicating a key role for Phactr-1 in tubulogenesis in vitro. In this study, we investigated the role of Phactr-1 in several cellular processes related to angiogenesis. We found that neuropilin-1 (NRP-1) and VEGF-R1 depletion inhibited Phactr-1 mRNA expression while NRP-2 and VEGF-R2 depletion had no effect. We described a new interaction site of VEGF-A(165) to VEGF-R1 in peptides encoded by exons 7 and 8 of VEGF-A(165). The specific inhibition of VEGF-A(165) binding on NRP-1 and VEGF-R1 by ERTCRC and CDKPRR peptides decreased the Phactr-1 mRNA levels in HUVECs indicating that VEGF-A(165)-dependent regulation of Phactr-1 expression required both NRP-1 and VEGF-R1 receptors. In addition, upon VEGFA(165)-stimulation Phactr-1 promotes formation and maintenance of cellular tubes through NRP-1 and VEGFR1. Phactr-1 was previously identified as protein phosphatase 1 (PP1) alpha-interacting protein that possesses actin-binding domains. We showed that Phactr-1 depletion decreased PP1 activity, disrupted the fine-tuning of actin polymerization and impaired lamellipodial dynamics. Taken together our results strongly suggest that Phactr-1 is a key component in the angiogenic process. (C) 2011 Elsevier Inc. All rights reserved.

引用

页码：214 / 223

页数：10

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