Journal Article

DKFZ-2017-03471

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png The bipartite rac1 Guanine nucleotide exchange factor engulfment and cell motility 1/dedicator of cytokinesis 180 (elmo1/dock180) protects endothelial cells from apoptosis in blood vessel development.

Schäker, K. (First author)DKFZ* ; Bartsch, S. ; Patry, C. ; Stoll, S. J. ; Hillebrands, J.-L. ; Wieland, T. ; Kroll, J. (Last author)DKFZ*

2015
Soc. Bethesda, Md.

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Please use a persistent id in citations: doi:10.1074/jbc.M114.633701

Abstract: Engulfment and cell motility 1/dedicator of cytokinesis 180 (Elmo1/Dock180) is a bipartite guanine nucleotide exchange factor for the monomeric GTPase Ras-related C3 botulinum toxin substrate 1 (Rac1). Elmo1/Dock180 regulates Rac1 activity in a specific spatiotemporal manner in endothelial cells (ECs) during zebrafish development and acts downstream of the Netrin-1/Unc5-homolog B (Unc5B) signaling cascade. However, mechanistic details on the pathways by which Elmo1/Dock180 regulates endothelial function and vascular development remained elusive. In this study, we aimed to analyze the vascular function of Elmo1 and Dock180 in human ECs and during vascular development in zebrafish embryos. In vitro overexpression of Elmo1 and Dock180 in ECs reduced caspase-3/7 activity and annexin V-positive cell number upon induction of apoptosis. This protective effect of Elmo1 and Dock180 is mediated by activation of Rac1, p21-activated kinase (PAK) and AKT/protein kinase B (AKT) signaling. In zebrafish, Elmo1 and Dock180 overexpression reduced the total apoptotic cell and apoptotic EC number and promoted the formation of blood vessels during embryogenesis. In conclusion, Elmo1 and Dock180 protect ECs from apoptosis by the activation of the Rac1/PAK/AKT signaling cascade in vitro and in vivo. Thus, Elmo1 and Dock180 facilitate blood vessel formation by stabilization of the endothelium during angiogenesis.

Keyword(s): Adaptor Proteins, Signal Transducing ; DOCK1 protein, human ; ELMO1 protein, human ; Guanine Nucleotide Exchange Factors ; RAC1 protein, human ; rac GTP-Binding Proteins ; rac1 GTP-Binding Protein

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Contributing Institute(s):

1. Vaskuläre Onkologie und Metastasierung (A190)

Research Program(s):

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

Appears in the scientific report 2015

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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

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