uPARAP/Endo180 receptor is a gatekeeper of VEGFR-2/VEGFR-3 heterodimerisation during pathological lymphangiogenesis

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Standard

uPARAP/Endo180 receptor is a gatekeeper of VEGFR-2/VEGFR-3 heterodimerisation during pathological lymphangiogenesis. / Durré, Tania; Morfoisse, Florent; Erpicum, Charlotte; Ebroin, Marie; Blacher, Silvia; García-Caballero, Melissa; Deroanne, Christophe; Louis, Thomas; Balsat, Cédric; Van de Velde, Maureen; Kaijalainen, Seppo; Kridelka, Frédéric; Engelholm, Lars; Struman, Ingrid; Alitalo, Kari; Behrendt, Niels; Paupert, Jenny; Noel, Agnès.

I: Nature Communications, Bind 9, Nr. 1, 5178, 05.12.2018, s. 1-16.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Durré, T, Morfoisse, F, Erpicum, C, Ebroin, M, Blacher, S, García-Caballero, M, Deroanne, C, Louis, T, Balsat, C, Van de Velde, M, Kaijalainen, S, Kridelka, F, Engelholm, L, Struman, I, Alitalo, K, Behrendt, N, Paupert, J & Noel, A 2018, 'uPARAP/Endo180 receptor is a gatekeeper of VEGFR-2/VEGFR-3 heterodimerisation during pathological lymphangiogenesis', Nature Communications, bind 9, nr. 1, 5178, s. 1-16. https://doi.org/10.1038/s41467-018-07514-1

APA

Durré, T., Morfoisse, F., Erpicum, C., Ebroin, M., Blacher, S., García-Caballero, M., Deroanne, C., Louis, T., Balsat, C., Van de Velde, M., Kaijalainen, S., Kridelka, F., Engelholm, L., Struman, I., Alitalo, K., Behrendt, N., Paupert, J., & Noel, A. (2018). uPARAP/Endo180 receptor is a gatekeeper of VEGFR-2/VEGFR-3 heterodimerisation during pathological lymphangiogenesis. Nature Communications, 9(1), 1-16. [5178]. https://doi.org/10.1038/s41467-018-07514-1

Vancouver

Durré T, Morfoisse F, Erpicum C, Ebroin M, Blacher S, García-Caballero M o.a. uPARAP/Endo180 receptor is a gatekeeper of VEGFR-2/VEGFR-3 heterodimerisation during pathological lymphangiogenesis. Nature Communications. 2018 dec. 5;9(1):1-16. 5178. https://doi.org/10.1038/s41467-018-07514-1

Author

Durré, Tania ; Morfoisse, Florent ; Erpicum, Charlotte ; Ebroin, Marie ; Blacher, Silvia ; García-Caballero, Melissa ; Deroanne, Christophe ; Louis, Thomas ; Balsat, Cédric ; Van de Velde, Maureen ; Kaijalainen, Seppo ; Kridelka, Frédéric ; Engelholm, Lars ; Struman, Ingrid ; Alitalo, Kari ; Behrendt, Niels ; Paupert, Jenny ; Noel, Agnès. / uPARAP/Endo180 receptor is a gatekeeper of VEGFR-2/VEGFR-3 heterodimerisation during pathological lymphangiogenesis. I: Nature Communications. 2018 ; Bind 9, Nr. 1. s. 1-16.

Bibtex

@article{08a397614e604ec582c928935974e5bd,
title = "uPARAP/Endo180 receptor is a gatekeeper of VEGFR-2/VEGFR-3 heterodimerisation during pathological lymphangiogenesis",
abstract = "The development of new lymphatic vessels occurs in many cancerous and inflammatory diseases through the binding of VEGF-C to its receptors, VEGFR-2 and VEGFR-3. The regulation of VEGFR-2/VEGFR-3 heterodimerisation and its downstream signaling in lymphatic endothelial cells (LECs) remain poorly understood. Here, we identify the endocytic receptor, uPARAP, as a partner of VEGFR-2 and VEGFR-3 that regulates their heterodimerisation. Genetic ablation of uPARAP leads to hyperbranched lymphatic vasculatures in pathological conditions without affecting concomitant angiogenesis. In vitro, uPARAP controls LEC migration in response to VEGF-C but not VEGF-A or VEGF-CCys156Ser. uPARAP restricts VEGFR-2/VEGFR-3 heterodimerisation and subsequent VEGFR-2-mediated phosphorylation and inactivation of Crk-II adaptor. uPARAP promotes VEGFR-3 signaling through the Crk-II/JNK/paxillin/Rac1 pathway. Pharmacological Rac1 inhibition in uPARAP knockout mice restores the wild-type phenotype. In summary, our study identifies a molecular regulator of lymphangiogenesis, and uncovers novel molecular features of VEGFR-2/VEGFR-3 crosstalk and downstream signaling during VEGF-C-driven LEC sprouting in pathological conditions.",
author = "Tania Durr{\'e} and Florent Morfoisse and Charlotte Erpicum and Marie Ebroin and Silvia Blacher and Melissa Garc{\'i}a-Caballero and Christophe Deroanne and Thomas Louis and C{\'e}dric Balsat and {Van de Velde}, Maureen and Seppo Kaijalainen and Fr{\'e}d{\'e}ric Kridelka and Lars Engelholm and Ingrid Struman and Kari Alitalo and Niels Behrendt and Jenny Paupert and Agn{\`e}s Noel",
year = "2018",
month = dec,
day = "5",
doi = "10.1038/s41467-018-07514-1",
language = "English",
volume = "9",
pages = "1--16",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "nature publishing group",
number = "1",

}

RIS

TY - JOUR

T1 - uPARAP/Endo180 receptor is a gatekeeper of VEGFR-2/VEGFR-3 heterodimerisation during pathological lymphangiogenesis

AU - Durré, Tania

AU - Morfoisse, Florent

AU - Erpicum, Charlotte

AU - Ebroin, Marie

AU - Blacher, Silvia

AU - García-Caballero, Melissa

AU - Deroanne, Christophe

AU - Louis, Thomas

AU - Balsat, Cédric

AU - Van de Velde, Maureen

AU - Kaijalainen, Seppo

AU - Kridelka, Frédéric

AU - Engelholm, Lars

AU - Struman, Ingrid

AU - Alitalo, Kari

AU - Behrendt, Niels

AU - Paupert, Jenny

AU - Noel, Agnès

PY - 2018/12/5

Y1 - 2018/12/5

N2 - The development of new lymphatic vessels occurs in many cancerous and inflammatory diseases through the binding of VEGF-C to its receptors, VEGFR-2 and VEGFR-3. The regulation of VEGFR-2/VEGFR-3 heterodimerisation and its downstream signaling in lymphatic endothelial cells (LECs) remain poorly understood. Here, we identify the endocytic receptor, uPARAP, as a partner of VEGFR-2 and VEGFR-3 that regulates their heterodimerisation. Genetic ablation of uPARAP leads to hyperbranched lymphatic vasculatures in pathological conditions without affecting concomitant angiogenesis. In vitro, uPARAP controls LEC migration in response to VEGF-C but not VEGF-A or VEGF-CCys156Ser. uPARAP restricts VEGFR-2/VEGFR-3 heterodimerisation and subsequent VEGFR-2-mediated phosphorylation and inactivation of Crk-II adaptor. uPARAP promotes VEGFR-3 signaling through the Crk-II/JNK/paxillin/Rac1 pathway. Pharmacological Rac1 inhibition in uPARAP knockout mice restores the wild-type phenotype. In summary, our study identifies a molecular regulator of lymphangiogenesis, and uncovers novel molecular features of VEGFR-2/VEGFR-3 crosstalk and downstream signaling during VEGF-C-driven LEC sprouting in pathological conditions.

AB - The development of new lymphatic vessels occurs in many cancerous and inflammatory diseases through the binding of VEGF-C to its receptors, VEGFR-2 and VEGFR-3. The regulation of VEGFR-2/VEGFR-3 heterodimerisation and its downstream signaling in lymphatic endothelial cells (LECs) remain poorly understood. Here, we identify the endocytic receptor, uPARAP, as a partner of VEGFR-2 and VEGFR-3 that regulates their heterodimerisation. Genetic ablation of uPARAP leads to hyperbranched lymphatic vasculatures in pathological conditions without affecting concomitant angiogenesis. In vitro, uPARAP controls LEC migration in response to VEGF-C but not VEGF-A or VEGF-CCys156Ser. uPARAP restricts VEGFR-2/VEGFR-3 heterodimerisation and subsequent VEGFR-2-mediated phosphorylation and inactivation of Crk-II adaptor. uPARAP promotes VEGFR-3 signaling through the Crk-II/JNK/paxillin/Rac1 pathway. Pharmacological Rac1 inhibition in uPARAP knockout mice restores the wild-type phenotype. In summary, our study identifies a molecular regulator of lymphangiogenesis, and uncovers novel molecular features of VEGFR-2/VEGFR-3 crosstalk and downstream signaling during VEGF-C-driven LEC sprouting in pathological conditions.

UR - http://www.scopus.com/inward/record.url?scp=85057967829&partnerID=8YFLogxK

U2 - 10.1038/s41467-018-07514-1

DO - 10.1038/s41467-018-07514-1

M3 - Journal article

C2 - 30518756

AN - SCOPUS:85057967829

VL - 9

SP - 1

EP - 16

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 5178

ER -

ID: 222250250