PUBLICATION
Marcksl1 modulates endothelial cell mechanoresponse to haemodynamic forces to control blood vessel shape and size
- Authors
- Kondrychyn, I., Kelly, D.J., Carretero, N.T., Nomori, A., Kato, K., Chong, J., Nakajima, H., Okuda, S., Mochizuki, N., Phng, L.K.
- ID
- ZDB-PUB-201120-1
- Date
- 2020
- Source
- Nature communications 11: 5476 (Journal)
- Registered Authors
- Chong, Jeronica, Kelly, Douglas, Kondrychyn, Igor, Mochizuki, Naoki, Nakajima, Hiroyuki, Nomori, Akane, Phng, Li-Kun
- Keywords
- none
- MeSH Terms
-
- Actins/metabolism
- Actomyosin/metabolism
- Animals
- Animals, Genetically Modified
- Blood Vessels/anatomy & histology*
- Blood Vessels/cytology
- Blood Vessels/physiology*
- Calmodulin-Binding Proteins/genetics
- Calmodulin-Binding Proteins/metabolism*
- Endothelial Cells/cytology
- Endothelial Cells/metabolism*
- Gene Expression Regulation, Developmental
- Hemodynamics/physiology*
- Microfilament Proteins/genetics
- Microfilament Proteins/metabolism*
- Models, Animal
- Transcriptome
- Zebrafish/embryology
- PubMed
- 33127887 Full text @ Nat. Commun.
Citation
Kondrychyn, I., Kelly, D.J., Carretero, N.T., Nomori, A., Kato, K., Chong, J., Nakajima, H., Okuda, S., Mochizuki, N., Phng, L.K. (2020) Marcksl1 modulates endothelial cell mechanoresponse to haemodynamic forces to control blood vessel shape and size. Nature communications. 11:5476.
Abstract
The formation of vascular tubes is driven by extensive changes in endothelial cell (EC) shape. Here, we have identified a role of the actin-binding protein, Marcksl1, in modulating the mechanical properties of EC cortex to regulate cell shape and vessel structure during angiogenesis. Increasing and depleting Marcksl1 expression level in vivo results in an increase and decrease, respectively, in EC size and the diameter of microvessels. Furthermore, endothelial overexpression of Marcksl1 induces ectopic blebbing on both apical and basal membranes, during and after lumen formation, that is suppressed by reduced blood flow. High resolution imaging reveals that Marcksl1 promotes the formation of linear actin bundles and decreases actin density at the EC cortex. Our findings demonstrate that a balanced network of linear and branched actin at the EC cortex is essential in conferring cortical integrity to resist the deforming forces of blood flow to regulate vessel structure.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping