Lanahan, A;
Zhang, X;
Fantin, A;
Zhuang, Z;
Rivera-Molina, F;
Speichinger, K;
Prahst, C;
... Simons, M; + view all
(2013)
The neuropilin 1 cytoplasmic domain is required for VEGF-A-dependent arteriogenesis.
Dev Cell
, 25
(2)
156 - 168.
10.1016/j.devcel.2013.03.019.
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Abstract
Neuropilin 1 (NRP1) plays an important but ill-defined role in VEGF-A signaling and vascular morphogenesis. We show that mice with a knockin mutation that ablates the NRP1 cytoplasmic tail (Nrp1(cyto)) have normal angiogenesis but impaired developmental and adult arteriogenesis. The arteriogenic defect was traced to the absence of a PDZ-dependent interaction between NRP1 and VEGF receptor 2 (VEGFR2) complex and synectin, which delayed trafficking of endocytosed VEGFR2 from Rab5+ to EAA1+ endosomes. This led to increased PTPN1 (PTP1b)-mediated dephosphorylation of VEGFR2 at Y(1175), the site involved in activating ERK signaling. The Nrp1(cyto) mutation also impaired endothelial tubulogenesis in vitro, which could be rescued by expressing full-length NRP1 or constitutively active ERK. These results demonstrate that the NRP1 cytoplasmic domain promotes VEGFR2 trafficking in a PDZ-dependent manner to regulate arteriogenic ERK signaling and establish a role for NRP1 in VEGF-A signaling during vascular morphogenesis.
| Type: | Article |
|---|---|
| Title: | The neuropilin 1 cytoplasmic domain is required for VEGF-A-dependent arteriogenesis. |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.devcel.2013.03.019 |
| Publisher version: | http://dx.doi.org/10.1016/j.devcel.2013.03.019 |
| Language: | English |
| Additional information: | © 2013 Elsevier Inc. This work is licensed under a Creative Commons Attribution 3.0 Unported License. PMCID: PMC3774154 |
| Keywords: | Animals, Arteries, Cells, Cultured, Cytoplasm, Endocytosis, Endosomes, Endothelium, Vascular, MAP Kinase Signaling System, Mice, Morphogenesis, Neovascularization, Pathologic, Neuropilin-1, Phosphorylation, Signal Transduction, Transferrin, Vascular Endothelial Growth Factor A, Vascular Endothelial Growth Factor Receptor-2, Vesicular Transport Proteins |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1392628 |
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