Journal Article

DKFZ-2017-05597

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Endothelial RSPO3 Controls Vascular Stability and Pruning through Non-canonical WNT/Ca(2+)/NFAT Signaling.

Scholz, B. (First author)DKFZ* ; Korn, C.DKFZ* ; Wojtarowicz, J.DKFZ* ; Mogler, C.DKFZ* ; Augustin, I.DKFZ* ; Boutros, M.DKFZ* ; Niehrs, C.DKFZ* ; Augustin, H. (Last author)DKFZ*

2016
Cell Press Cambridge, Mass.

This record in other databases:  

Please use a persistent id in citations: doi:10.1016/j.devcel.2015.12.015

Abstract: The WNT signaling enhancer R-spondin3 (RSPO3) is prominently expressed in the vasculature. Correspondingly, embryonic lethality of Rspo3-deficient mice is caused by vessel remodeling defects. Yet the mechanisms underlying vascular RSPO3 function remain elusive. Inducible endothelial Rspo3 deletion (Rspo3-iECKO) resulted in perturbed developmental and tumor vascular remodeling. Endothelial cell apoptosis and vascular pruning led to reduced microvessel density in Rspo3-iECKO mice. Rspo3-iECKO mice strikingly phenocopied the non-canonical WNT signaling-induced vascular defects of mice deleted for the WNT secretion factor Evi/Wls. An endothelial screen for RSPO3 and EVI/WLS co-regulated genes identified Rnf213, Usp18, and Trim30α. RNF213 targets filamin A and NFAT1 for proteasomal degradation attenuating non-canonical WNT/Ca(2+) signaling. Likewise, USP18 and TRIM5α inhibited NFAT1 activation. Consequently, NFAT protein levels were decreased in endothelial cells of Rspo3-iECKO mice and pharmacological NFAT inhibition phenocopied Rspo3-iECKO mice. The data identify endothelial RSPO3-driven non-canonical WNT/Ca(2+)/NFAT signaling as a critical maintenance pathway of the remodeling vasculature.

Keyword(s): NFATC Transcription Factors ; R-spondin3 protein, mouse ; Thrombospondins ; Transcription Factors ; Wnt Proteins ; Calcium

---

Contributing Institute(s):

1. Vaskuläre Onkologie und Metastasierung (A190)
2. Signalwege und Funktionelle Genomik (B110)
3. Molekulare Embryologie (A050)
4. DKTK Heidelberg (L101)

Research Program(s):

1. 321 - Basic Concepts (POF3-321) (POF3-321)

Appears in the scientific report 2016

---

Database coverage:
; BIOSIS Previews ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF >= 5 ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection

---