Neuropilin 1 and its inhibitory ligand mini-tryptophanyl-tRNA synthetase inversely regulate VE-cadherin turnover and vascular permeability

Noemi Gioelli, Lisa J. Neilson, Na Wei, Giulia Villari, Wenqian Chen, Bernhard Kuhle, Manuel Ehling, Federica Maione, Sander Willox, Serena Brundu, Daniele Avanzato, Grigorios Koulouras, Massimiliano Mazzone, Enrico Giraudo, Xiang-Lei Yang, Donatella Valdembri, Sara Zanivan () and Guido Serini ()
Additional contact information
Noemi Gioelli: University of Torino School of Medicine
Lisa J. Neilson: Cancer Research UK Beatson Institute
Na Wei: The Scripps Research Institute
Giulia Villari: University of Torino School of Medicine
Wenqian Chen: The Scripps Research Institute
Bernhard Kuhle: The Scripps Research Institute
Manuel Ehling: University of Leuven
Federica Maione: University of Torino School of Medicine
Sander Willox: University of Leuven
Serena Brundu: Candiolo Cancer Institute - Fondazione del Piemonte per l’Oncologia (FPO) Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS)
Daniele Avanzato: University of Torino School of Medicine
Grigorios Koulouras: Cancer Research UK Beatson Institute
Massimiliano Mazzone: University of Leuven
Enrico Giraudo: Candiolo Cancer Institute - Fondazione del Piemonte per l’Oncologia (FPO) Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS)
Xiang-Lei Yang: The Scripps Research Institute
Donatella Valdembri: University of Torino School of Medicine
Sara Zanivan: Cancer Research UK Beatson Institute
Guido Serini: University of Torino School of Medicine

Nature Communications, 2022, vol. 13, issue 1, 1-16

Abstract: Abstract The formation of a functional blood vessel network relies on the ability of endothelial cells (ECs) to dynamically rearrange their adhesive contacts in response to blood flow and guidance cues, such as vascular endothelial growth factor-A (VEGF-A) and class 3 semaphorins (SEMA3s). Neuropilin 1 (NRP1) is essential for blood vessel development, independently of its ligands VEGF-A and SEMA3, through poorly understood mechanisms. Grounding on unbiased proteomic analysis, we report here that NRP1 acts as an endocytic chaperone primarily for adhesion receptors on the surface of unstimulated ECs. NRP1 localizes at adherens junctions (AJs) where, interacting with VE-cadherin, promotes its basal internalization-dependent turnover and favors vascular permeability initiated by histamine in both cultured ECs and mice. We identify a splice variant of tryptophanyl-tRNA synthetase (mini-WARS) as an unconventionally secreted extracellular inhibitory ligand of NRP1 that, by stabilizing it at the AJs, slows down both VE-cadherin turnover and histamine-elicited endothelial leakage. Thus, our work shows a role for NRP1 as a major regulator of AJs plasticity and reveals how mini-WARS acts as a physiological NRP1 inhibitory ligand in the control of VE-cadherin endocytic turnover and vascular permeability.

Date: 2022
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-022-31904-1 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31904-1

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-022-31904-1

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().