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ZFIN ID: ZDB-PUB-150526-5
Polo-like kinase 2 regulates angiogenic sprouting and blood vessel development
Yang, H., Fang, L., Zhan, R., Hegarty, J.M., Ren, J., Hsiai, T.K., Gleeson, J.G., Miller, Y.I., Trejo, J., Chi, N.C.
Date: 2015
Source: Developmental Biology 404(2): 49-60 (Journal)
Registered Authors: Hegarty, Jeff, Miller, Yury, Yang, Hongbo
Keywords: Angiogenesis, Human Umbilical Vein Endothelial Cells, Polo-like kinase 2, Vascular development, Zebrafish
MeSH Terms:
  • Animals
  • Cell Line
  • Cell Movement/genetics
  • Cell Proliferation/genetics
  • Guanine Nucleotide Exchange Factors/metabolism
  • Human Umbilical Vein Endothelial Cells/metabolism*
  • Humans
  • Neovascularization, Physiologic/genetics*
  • Nerve Tissue Proteins/metabolism
  • Protein-Serine-Threonine Kinases/biosynthesis
  • Protein-Serine-Threonine Kinases/genetics*
  • Protein-Serine-Threonine Kinases/metabolism
  • Pseudopodia/metabolism
  • RNA Interference
  • RNA, Small Interfering
  • Signal Transduction
  • Zebrafish/embryology*
  • rap1 GTP-Binding Proteins/metabolism*
PubMed: 26004360 Full text @ Dev. Biol.
FIGURES
ABSTRACT
Angiogenesis relies on specialized endothelial tip cells to extend toward guidance cues in order to direct growing blood vessels. Although many of the signaling pathways that control this directional endothelial sprouting are well known, the specific cellular mechanisms that mediate this process remain to be fully elucidated. Here, we show that Polo-like kinase 2 (PLK2) regulates Rap1 activity to guide endothelial tip cell lamellipodia formation and subsequent angiogenic sprouting. Using a combination of high-resolution in vivo imaging of zebrafish vascular development and a human umbilical vein endothelial cell (HUVEC) in vitro cell culture system, we observed that loss of PLK2 function resulted in a reduction in endothelial cell sprouting and migration, whereas overexpression of PLK2 promoted angiogenesis. Furthermore, we discovered that PLK2 may control angiogenic sprouting by binding to PDZ-GEF to regulate RAP1 activity during endothelial cell lamellipodia formation and extracellular matrix attachment. Consistent with these findings, constitutively active RAP1 could rescue the endothelial cell sprouting defects observed in zebrafish and HUVEC PLK2 knockdowns. Overall, these findings reveal a conserved PLK2-RAP1 pathway that is crucial to regulate endothelial tip cell behavior in order to ensure proper vascular development and patterning in vertebrates.
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