Mfsd2b and Spns2 are essential for maintenance of blood vessels during development and in anaphylactic shock.

Anaphylaxis / metabolism Animals Anion Transport Proteins / metabolism Biological Transport Endothelial Cells / metabolism Homeostasis Lysophospholipids / metabolism Membrane Proteins / metabolism Mice Sphingosine / metabolism
CP: Developmental biology CP: Molecular biology Mfsd2b S1P signaling S1P transporters Spns2 anaphylaxis embryonic lethality hemorrhage plasma S1P sphingolipids sphingosine kinases sphingosine-1-phosphate vascular homeostasis

Journal

Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691

Informations de publication

Date de publication:
16 08 2022
Historique:
received: 20 08 2021
revised: 23 05 2022
accepted: 21 07 2022
entrez: 17 8 2022
pubmed: 18 8 2022
medline: 20 8 2022
Statut: ppublish

Résumé

Sphingosine-1-phosphate (S1P) is a potent lipid mediator that is secreted by several cell types. We recently showed that Mfsd2b is an S1P transporter from hematopoietic cells that contributes approximately 50% plasma S1P. Here we report the characterization of compound deletion of Mfsd2b and Spns2, another S1P transporter active primarily in endothelial cells. Global deletion of Mfsd2b and Spns2 (global double knockout [gDKO]) results in embryonic lethality beyond embryonic day 14.5 (E14.5), with severe hemorrhage accompanied by defects of tight junction proteins, indicating that Mfsd2b and Spns2 provide S1P for signaling, which is essential for blood vessel integrity. Compound postnatal deletion of Mfsd2b and Spns2 using Mx1Cre (ctDKO-Mx1Cre) results in maximal 80% reduction of plasma S1P. ctDKO-Mx1Cre mice exhibit severe susceptibility to anaphylaxis, indicating that S1P from Mfsd2b and Spns2 is indispensable for vascular homeostasis. Our results show that S1P export from Mfsd2b and Spns2 is essential for developing and mature vasculature.

Identifiants

DOI: 10.1016/j.celrep.2022.111208 PMID: 35977478
pubmed: 35977478
pii: S2211-1247(22)01025-7
doi: 10.1016/j.celrep.2022.111208
pii:
doi:

Substances chimiques

Anion Transport Proteins 0
Lysophospholipids 0
Membrane Proteins 0
Mfsd2b protein, mouse 0
Spns2 protein, mouse 0
Sphingosine NGZ37HRE42

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

111208

Informations de copyright

Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests The authors declare no competing interests.

Auteurs

Thanh Nha Uyen Le (TNU)

Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117596, Singapore.

Toan Q Nguyen (TQ)

Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117596, Singapore.

Pazhanichamy Kalailingam (P)

Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117596, Singapore.

Yen Thi Kim Nguyen (YTK)

Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117596, Singapore.

Viresh Krishnan Sukumar (VK)

Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117596, Singapore.

Clarissa Kai Hui Tan (CKH)

Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117596, Singapore.

Farhana Tukijan (F)

Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117596, Singapore.

Ludovic Couty (L)

Université Paris Cité, PARCC, INSERM U970, 56 Rue Leblanc, 75015 Paris, France.

Zafrul Hasan (Z)

Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117596, Singapore.

Ilaria Del Gaudio (I)

Université Paris Cité, PARCC, INSERM U970, 56 Rue Leblanc, 75015 Paris, France.

Markus R Wenk (MR)

Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117596, Singapore; Singapore Lipidomics Incubator (SLING), Life Sciences Institute, National University of Singapore, Singapore 117456, Singapore.

Amaury Cazenave-Gassiot (A)

Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117596, Singapore; Singapore Lipidomics Incubator (SLING), Life Sciences Institute, National University of Singapore, Singapore 117456, Singapore.

Eric Camerer (E)

Université Paris Cité, PARCC, INSERM U970, 56 Rue Leblanc, 75015 Paris, France.

Long N Nguyen (LN)

Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117596, Singapore; Singapore Lipidomics Incubator (SLING), Life Sciences Institute, National University of Singapore, Singapore 117456, Singapore; Cardiovascular Disease Research (CVD) Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117545, Singapore; Immunology Program, Life Sciences Institute, National University of Singapore, Singapore 117456, Singapore; Immunology Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117456, Singapore. Electronic address: bchnnl@nus.edu.sg.

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Classifications MeSH

questionsmedicales.fr › Maladies du système immunitaire › Hypersensibilité › Hypersensibilité immédiate › Anaphylaxie › Mfsd2b and Spns2 are essential for maintenance...
questionsmedicales.fr › Eucaryotes › Animaux › Mfsd2b and Spns2 are essential for maintenance...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Protéines de transport membranaire › Pompes ioniques › Transporteurs d'anions › Mfsd2b and Spns2 are essential for maintenance...
questionsmedicales.fr › Métabolisme › Transport biologique › Mfsd2b and Spns2 are essential for maintenance...
questionsmedicales.fr › Cellules › Cellules épithéliales › Cellules endothéliales › Mfsd2b and Spns2 are essential for maintenance...
questionsmedicales.fr › Phénomènes physiologiques › Homéostasie › Mfsd2b and Spns2 are essential for maintenance...
questionsmedicales.fr › Lipides › Lipides membranaires › Phospholipides › Glycérophosphate › Acides phosphatidiques › Lysophospholipides › Mfsd2b and Spns2 are essential for maintenance...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Mfsd2b and Spns2 are essential for maintenance...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Mfsd2b and Spns2 are essential for maintenance...
questionsmedicales.fr › Composés chimiques organiques › Amines › Aminoalcools › Sphingosine › Mfsd2b and Spns2 are essential for maintenance...