Marcksl1 modulates endothelial cell mechanoresponse to haemodynamic forces to control blood vessel shape and size
| Autor: | Jeronica Chong, Douglas J. Kelly, Naoki Mochizuki, Akane Nomori, Igor Kondrychyn, Hiroyuki Nakajima, Li-Kun Phng, Satoru Okuda, Núria Taberner Carretero, Kagayaki Kato |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cell biology Angiogenesis Science General Physics and Astronomy General Biochemistry Genetics and Molecular Biology Article Animals Genetically Modified 03 medical and health sciences 0302 clinical medicine In vivo Cortex (anatomy) Developmental biology medicine Animals lcsh:Science Actin Zebrafish Multidisciplinary Chemistry Microfilament Proteins Hemodynamics Endothelial Cells Gene Expression Regulation Developmental General Chemistry Actomyosin Blood flow Actins eye diseases Endothelial stem cell 030104 developmental biology medicine.anatomical_structure Models Animal Biophysics Blood Vessels Calmodulin-Binding Proteins lcsh:Q sense organs Transcriptome 030217 neurology & neurosurgery Lumen (unit) Blood vessel |
| Zdroj: | Nature Communications, Vol 11, Iss 1, Pp 1-18 (2020) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | 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. During lumen formation in blood vessels, endothelial cells become exposed to hemodynamic forces that induce membrane blebbing and changes in cell shape. Here, the authors show endothelial cells develop an actin-based protective mechanism in the cell cortex that prevents excessive blebbing to control cell shape and vessel diameter. |
| Databáze: | OpenAIRE |
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