Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Heterotypic inter-GPCR ß-arrestin coupling regulates lymphatic endothelial junctional architecture in murine lymph nodes

Yu Hisano, Mari Kono, Eric Engelbrecht, Koki Kawakami, Keisuke Yanagida, Andreane Cartier, Sylvain Galvani, Andrew Kuo, Yuki Ono, Satoru Ishida, Junken Aoki, Richard L. Proia, Asuka Inoue, View ORCID ProfileTimothy Hla
doi: https://doi.org/10.1101/435776
Yu Hisano
Vascular Biology Program, Boston Children’s Hospital, Department of Surgery, Harvard Medical School, Boston, MA 02215, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mari Kono
Genetics and Development Branch, NIDDK, NIH, Bethesda, MD
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Eric Engelbrecht
Vascular Biology Program, Boston Children’s Hospital, Department of Surgery, Harvard Medical School, Boston, MA 02215, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Koki Kawakami
Department of Pharmacology, Tohoku University, Sendai, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Keisuke Yanagida
Vascular Biology Program, Boston Children’s Hospital, Department of Surgery, Harvard Medical School, Boston, MA 02215, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Andreane Cartier
Vascular Biology Program, Boston Children’s Hospital, Department of Surgery, Harvard Medical School, Boston, MA 02215, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sylvain Galvani
Vascular Biology Program, Boston Children’s Hospital, Department of Surgery, Harvard Medical School, Boston, MA 02215, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Andrew Kuo
Vascular Biology Program, Boston Children’s Hospital, Department of Surgery, Harvard Medical School, Boston, MA 02215, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yuki Ono
Department of Pharmacology, Tohoku University, Sendai, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Satoru Ishida
Department of Pharmacology, Tohoku University, Sendai, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Junken Aoki
Department of Pharmacology, Tohoku University, Sendai, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Richard L. Proia
Genetics and Development Branch, NIDDK, NIH, Bethesda, MD
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Asuka Inoue
Department of Pharmacology, Tohoku University, Sendai, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Timothy Hla
Vascular Biology Program, Boston Children’s Hospital, Department of Surgery, Harvard Medical School, Boston, MA 02215, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Timothy Hla
  • For correspondence: timothy.hla@childrens.harvard.edu
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

Abstract

Lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P) activate G protein-coupled receptors (GPCRs) to regulate key pathobiological processes. Here we report a novel lipid mediator GPCR cross-talk mechanism that modulates lymphatic endothelial junctional architecture in lymph nodes. LPAR1 was identified as an inducer of S1PR1/ ß-arrestin coupling from a genome-wide CRISPR/ Cas9 transcriptional activation screen. LPAR1 activation induced S1PR1 ß-arrestin recruitment while suppressing Gαi protein signaling. Lymphatic endothelial cells from cortical and medullary sinuses of lymph nodes which express LPAR1 and S1PR1, exhibit porous junctional architecture and constitutive S1PR1 coupling to ß-arrestin which was suppressed by the LPAR1 antagonist AM095. In endothelial cells, LPAR1-activation increased trans-endothelial permeability and junctional remodeling from zipper-like structures to puncta of adhesion plaques that terminate at actin-rich stress fibers with abundant intercellular gaps. Cross-talk between LPA and S1P receptors regulates complex junctional architecture of lymphatic sinus endothelial cells, a site of high lymphocyte traffic and lymph flow.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
Back to top
PreviousNext
Posted October 04, 2018.
Download PDF

Supplementary Material

Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Heterotypic inter-GPCR ß-arrestin coupling regulates lymphatic endothelial junctional architecture in murine lymph nodes
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
Share
Heterotypic inter-GPCR ß-arrestin coupling regulates lymphatic endothelial junctional architecture in murine lymph nodes
Yu Hisano, Mari Kono, Eric Engelbrecht, Koki Kawakami, Keisuke Yanagida, Andreane Cartier, Sylvain Galvani, Andrew Kuo, Yuki Ono, Satoru Ishida, Junken Aoki, Richard L. Proia, Asuka Inoue, Timothy Hla
bioRxiv 435776; doi: https://doi.org/10.1101/435776
Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
Citation Tools
Heterotypic inter-GPCR ß-arrestin coupling regulates lymphatic endothelial junctional architecture in murine lymph nodes
Yu Hisano, Mari Kono, Eric Engelbrecht, Koki Kawakami, Keisuke Yanagida, Andreane Cartier, Sylvain Galvani, Andrew Kuo, Yuki Ono, Satoru Ishida, Junken Aoki, Richard L. Proia, Asuka Inoue, Timothy Hla
bioRxiv 435776; doi: https://doi.org/10.1101/435776

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Cell Biology
Subject Areas
All Articles
  • Animal Behavior and Cognition (1533)
  • Biochemistry (2492)
  • Bioengineering (1747)
  • Bioinformatics (9700)
  • Biophysics (3915)
  • Cancer Biology (2979)
  • Cell Biology (4213)
  • Clinical Trials (135)
  • Developmental Biology (2639)
  • Ecology (4108)
  • Epidemiology (2033)
  • Evolutionary Biology (6911)
  • Genetics (5224)
  • Genomics (6519)
  • Immunology (2193)
  • Microbiology (6974)
  • Molecular Biology (2765)
  • Neuroscience (17348)
  • Paleontology (126)
  • Pathology (430)
  • Pharmacology and Toxicology (709)
  • Physiology (1062)
  • Plant Biology (2498)
  • Scientific Communication and Education (646)
  • Synthetic Biology (832)
  • Systems Biology (2691)
  • Zoology (433)