The angiogenic function of nucleolin is mediated by vascular endothelial growth factor and nonmuscle myosin.
Nucleolin, originally described as a nuclear protein, was recently found to be expressed on the surface of endothelial cells during angiogenic. However, the functions of cell-surface nucleolin in angiogenic remain mysterious. Here we report that upon endothelial cells adhering to extracellular matrix components, vascular endothelial growth factor (VEGF) mobilizes nucleolin from nucleus to cell surface. Functional blockage or down-regulation of the expression of cell-surface nucleolin in endothelial cells significantly inhibits the migration of endothelial cells and prevents capillary-tubule formation. Moreover, nonmuscle myosin heavy chain 9 (MyH9), an actin-based motor protein, is identified as a nucleolin-binding protein. Subsequent studies reveal that MyH9 serves as a physical linker between nucleolin and cytoskeleton, thus modulating the translocation of nucleolin. Knocking down endogenous MyH9, specifically inhibiting myosin activity, or overexpressing functional deficient MyH9 disrupts the organization of cell-surface nucleolin and inhibits its angiogenic function. These studies indicate that VEGF, extracellular matrix, and intracellular motor protein MyH9 are all essential for the novel function of nucleolin in angiogenic.
Huang
Yujie
Y
Laboratory of Protein Chemistry, Department of Biological Sciences and Biotechnology, Tsinghua University, Beijing 100084, PR China.
Shi
Hubing
H
Zhou
Hao
H
Song
Xiaomin
X
Yuan
Shaopeng
S
Luo
Yongzhang
Y
D021581:Active Transport, Cell Nucleus; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D020409:Molecular Motor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D018995:Myosin Heavy Chains / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D018919:Neovascularization, Physiologic; D010750:Phosphoproteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D034622:RNA Interference; D016601:RNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology*; D000097796:Nucleolin
D020409:Molecular Motor Proteins; D018995:Myosin Heavy Chains; D010750:Phosphoproteins; D016601:RNA-Binding Proteins; D042461:Vascular Endothelial Growth Factor A; D000097796:Nucleolin; C103814:MYH9 protein, human; C467484:VEGFA protein, human