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

Barbara Allain; Rafika Jarray; Lucia Borriello; Bertrand Leforban; Sylvie Dufour; Wang Qing Liu; Perayot Pamonsinlapatham; Sara Bianco; Jérôme Larghero; Reda Hadj-Slimane; Christiane Garbay; Franҫoise Raynaud; Yves Lepelletier

doi:10.1016/j.cellsig.2011.09.003

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

Barbara Allain, Rafika Jarray, Lucia Borriello, Bertrand Leforban, Sylvie Dufour, Wang Qing Liu, Perayot Pamonsinlapatham, Sara Bianco, Jérôme Larghero, Reda Hadj-Slimane, Christiane Garbay, Franҫoise Raynaud, Yves Lepelletier

Cancer Signaling and Microenvironment (CSM)

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Abstract

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) α-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.

Original language	English
Pages (from-to)	214-223
Number of pages	10
Journal	Cellular Signalling
Volume	24
Issue number	1
DOIs	https://doi.org/10.1016/j.cellsig.2011.09.003
State	Published - Jan 2012

Keywords

Amino Acid Sequence
Binding, Competitive
Cell Culture Techniques
Cell Movement
Cells, Cultured
Endothelial Cells/metabolism
Gene Knockdown Techniques
Human Umbilical Vein Endothelial Cells/metabolism
Humans
Microfilament Proteins/genetics
Microtubules/metabolism
Neovascularization, Pathologic/metabolism
Neuropilin-1/genetics
Peptide Fragments/chemistry
Protein Binding
Pseudopodia/metabolism
RNA Interference
Time-Lapse Imaging
Transcription, Genetic
Vascular Endothelial Growth Factor A/chemistry
Vascular Endothelial Growth Factor Receptor-1/chemistry

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10.1016/j.cellsig.2011.09.003

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Allain, B., Jarray, R., Borriello, L., Leforban, B., Dufour, S., Liu, W. Q., Pamonsinlapatham, P., Bianco, S., Larghero, J., Hadj-Slimane, R., Garbay, C., Raynaud, F., & Lepelletier, Y. (2012). Neuropilin-1 regulates a new VEGF-induced gene, Phactr-1, which controls tubulogenesis and modulates lamellipodial dynamics in human endothelial cells. Cellular Signalling, 24(1), 214-223. https://doi.org/10.1016/j.cellsig.2011.09.003

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

abstract = "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) α-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.",

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author = "Barbara Allain and Rafika Jarray and Lucia Borriello and Bertrand Leforban and Sylvie Dufour and Liu, \{Wang Qing\} and Perayot Pamonsinlapatham and Sara Bianco and J{\'e}r{\^o}me Larghero and Reda Hadj-Slimane and Christiane Garbay and Franҫoise Raynaud and Yves Lepelletier",

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Allain, B, Jarray, R, Borriello, L, Leforban, B, Dufour, S, Liu, WQ, Pamonsinlapatham, P, Bianco, S, Larghero, J, Hadj-Slimane, R, Garbay, C, Raynaud, F & Lepelletier, Y 2012, 'Neuropilin-1 regulates a new VEGF-induced gene, Phactr-1, which controls tubulogenesis and modulates lamellipodial dynamics in human endothelial cells', Cellular Signalling, vol. 24, no. 1, pp. 214-223. https://doi.org/10.1016/j.cellsig.2011.09.003

TY - JOUR

T1 - Neuropilin-1 regulates a new VEGF-induced gene, Phactr-1, which controls tubulogenesis and modulates lamellipodial dynamics in human endothelial cells

AU - Allain, Barbara

AU - Jarray, Rafika

AU - Borriello, Lucia

AU - Leforban, Bertrand

AU - Dufour, Sylvie

AU - Liu, Wang Qing

AU - Pamonsinlapatham, Perayot

AU - Bianco, Sara

AU - Larghero, Jérôme

AU - Hadj-Slimane, Reda

AU - Garbay, Christiane

AU - Raynaud, Franҫoise

AU - Lepelletier, Yves

PY - 2012/1

Y1 - 2012/1

N2 - 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) α-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.

AB - 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) α-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.

KW - Amino Acid Sequence

KW - Binding, Competitive

KW - Cell Culture Techniques

KW - Cell Movement

KW - Cells, Cultured

KW - Endothelial Cells/metabolism

KW - Gene Knockdown Techniques

KW - Human Umbilical Vein Endothelial Cells/metabolism

KW - Humans

KW - Microfilament Proteins/genetics

KW - Microtubules/metabolism

KW - Neovascularization, Pathologic/metabolism

KW - Neuropilin-1/genetics

KW - Peptide Fragments/chemistry

KW - Protein Binding

KW - Pseudopodia/metabolism

KW - RNA Interference

KW - Time-Lapse Imaging

KW - Transcription, Genetic

KW - Vascular Endothelial Growth Factor A/chemistry

KW - Vascular Endothelial Growth Factor Receptor-1/chemistry

UR - https://www.scopus.com/pages/publications/80755132107

U2 - 10.1016/j.cellsig.2011.09.003

DO - 10.1016/j.cellsig.2011.09.003

M3 - Article

C2 - 21939755

SN - 0898-6568

VL - 24

SP - 214

EP - 223

JO - Cellular Signalling

JF - Cellular Signalling

IS - 1

ER -

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

Abstract

Keywords

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