PUBLICATION
Excess centrosomes disrupt vascular lumenization and endothelial cell adherens junctions
- Authors
- Buglak, D.B., Kushner, E.J., Marvin, A.P., Davis, K.L., Bautch, V.L.
- ID
- ZDB-PUB-200724-23
- Date
- 2020
- Source
- Angiogenesis 23(4): 567-575 (Journal)
- Registered Authors
- Kushner, Erich
- Keywords
- Angiogenesis, Centrosome, Endothelial cell, Junctions, Lumen, Polarity
- MeSH Terms
-
- Adherens Junctions/metabolism*
- Animals
- Blood Vessels/metabolism*
- Cell Polarity
- Centrosome/metabolism*
- Human Umbilical Vein Endothelial Cells/metabolism*
- Humans
- Neovascularization, Physiologic
- Zebrafish
- Zebrafish Proteins/metabolism
- PubMed
- 32699963 Full text @ Angiogenesis
Citation
Buglak, D.B., Kushner, E.J., Marvin, A.P., Davis, K.L., Bautch, V.L. (2020) Excess centrosomes disrupt vascular lumenization and endothelial cell adherens junctions. Angiogenesis. 23(4):567-575.
Abstract
Proper blood vessel formation requires coordinated changes in endothelial cell polarity and rearrangement of cell-cell junctions to form a functional lumen. One important regulator of cell polarity is the centrosome, which acts as a microtubule organizing center. Excess centrosomes perturb aspects of endothelial cell polarity linked to migration, but whether centrosome number influences apical-basal polarity and cell-cell junctions is unknown. Here, we show that excess centrosomes alter the apical-basal polarity of endothelial cells in angiogenic sprouts and disrupt endothelial cell-cell adherens junctions. Endothelial cells with excess centrosomes had narrower lumens in a 3D sprouting angiogenesis model, and zebrafish intersegmental vessels had reduced perfusion following centrosome overduplication. These results indicate that endothelial cell centrosome number regulates proper lumenization downstream of effects on apical-basal polarity and cell-cell junctions. Endothelial cells with excess centrosomes are prevalent in tumor vessels, suggesting how centrosomes may contribute to tumor vessel dysfunction.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping