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Polydom/SVEP1 binds to Tie1 and promotes migration of lymphatic endothelial cells

Polydom is an extracellular matrix protein involved in lymphatic vessel development. Polydom-deficient mice die immediately after birth due to defects in lymphatic vessel remodeling, but the mechanism involved is poorly understood. Here, we report that Polydom directly binds to Tie1, an orphan recep...

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Autores principales: Sato-Nishiuchi, Ryoko, Doiguchi, Masamichi, Morooka, Nanami, Sekiguchi, Kiyotoshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10281526/
https://www.ncbi.nlm.nih.gov/pubmed/37338522
http://dx.doi.org/10.1083/jcb.202208047
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author Sato-Nishiuchi, Ryoko
Doiguchi, Masamichi
Morooka, Nanami
Sekiguchi, Kiyotoshi
author_facet Sato-Nishiuchi, Ryoko
Doiguchi, Masamichi
Morooka, Nanami
Sekiguchi, Kiyotoshi
author_sort Sato-Nishiuchi, Ryoko
collection PubMed
description Polydom is an extracellular matrix protein involved in lymphatic vessel development. Polydom-deficient mice die immediately after birth due to defects in lymphatic vessel remodeling, but the mechanism involved is poorly understood. Here, we report that Polydom directly binds to Tie1, an orphan receptor in the Angiopoietin–Tie axis, and facilitates migration of lymphatic endothelial cells (LECs) in a Tie1-dependent manner. Polydom-induced LEC migration is diminished by PI3K inhibitors but not by an ERK inhibitor, suggesting that the PI3K/Akt signaling pathway is involved in Polydom-induced LEC migration. In line with this possibility, Akt phosphorylation in LECs is enhanced by Polydom although no significant Tie1 phosphorylation is induced by Polydom. LECs also exhibited nuclear exclusion of Foxo1, a signaling event downstream of Akt activation, which was impaired in Polydom-deficient mice. These findings indicate that Polydom is a physiological ligand for Tie1 and participates in lymphatic vessel development through activation of the PI3K/Akt pathway.
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spelling pubmed-102815262023-06-21 Polydom/SVEP1 binds to Tie1 and promotes migration of lymphatic endothelial cells Sato-Nishiuchi, Ryoko Doiguchi, Masamichi Morooka, Nanami Sekiguchi, Kiyotoshi J Cell Biol Article Polydom is an extracellular matrix protein involved in lymphatic vessel development. Polydom-deficient mice die immediately after birth due to defects in lymphatic vessel remodeling, but the mechanism involved is poorly understood. Here, we report that Polydom directly binds to Tie1, an orphan receptor in the Angiopoietin–Tie axis, and facilitates migration of lymphatic endothelial cells (LECs) in a Tie1-dependent manner. Polydom-induced LEC migration is diminished by PI3K inhibitors but not by an ERK inhibitor, suggesting that the PI3K/Akt signaling pathway is involved in Polydom-induced LEC migration. In line with this possibility, Akt phosphorylation in LECs is enhanced by Polydom although no significant Tie1 phosphorylation is induced by Polydom. LECs also exhibited nuclear exclusion of Foxo1, a signaling event downstream of Akt activation, which was impaired in Polydom-deficient mice. These findings indicate that Polydom is a physiological ligand for Tie1 and participates in lymphatic vessel development through activation of the PI3K/Akt pathway. Rockefeller University Press 2023-06-20 /pmc/articles/PMC10281526/ /pubmed/37338522 http://dx.doi.org/10.1083/jcb.202208047 Text en © 2023 Sato-Nishiuchi et al. https://creativecommons.org/licenses/by/4.0/This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sato-Nishiuchi, Ryoko
Doiguchi, Masamichi
Morooka, Nanami
Sekiguchi, Kiyotoshi
Polydom/SVEP1 binds to Tie1 and promotes migration of lymphatic endothelial cells
title Polydom/SVEP1 binds to Tie1 and promotes migration of lymphatic endothelial cells
title_full Polydom/SVEP1 binds to Tie1 and promotes migration of lymphatic endothelial cells
title_fullStr Polydom/SVEP1 binds to Tie1 and promotes migration of lymphatic endothelial cells
title_full_unstemmed Polydom/SVEP1 binds to Tie1 and promotes migration of lymphatic endothelial cells
title_short Polydom/SVEP1 binds to Tie1 and promotes migration of lymphatic endothelial cells
title_sort polydom/svep1 binds to tie1 and promotes migration of lymphatic endothelial cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10281526/
https://www.ncbi.nlm.nih.gov/pubmed/37338522
http://dx.doi.org/10.1083/jcb.202208047
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