title: Angiomotin-like2 gene (amotl2) is required for migration and proliferation of endothelial cells during angiogenesis.
abstract: Angiogenesis involves sprouting, migration, and proliferation of endothelial cells. The angiomotin-like2 gene (amotl2) has been found in blood vessels in zebrafish embryos, but its function in angiogenesis and underlying mechanisms remain unknown. In this study, we demonstrate that knockdown of amotl2 in zebrafish Tg(fli1:EGFP)(y1) and Tg(fli1:nEGFP)(y7) transgenic embryos impairs the intersegmental vessel growth and suppresses proliferation of endothelial cells. Transplantation experiments indicate that function of amotl2 in intersegmental vessel growth is cell-autonomous. AMOTL2 knockdown in cultured human umbilical vein endothelial cells also inhibits cell proliferation and migration and disrupts cell polarity, ultimately interrupting the formation of vascular tube-like structures. Amotl2 promotes MAPK/ERK activation via c-Src, which is dependent on phosphorylation of tyrosine residue at position 103 but independent of the C-terminal PDZ-binding domain. Taking together, our data indicate that Amotl2 plays a pivotal role in polarity, migration and proliferation of angiogenic endothelial cells.
authors.affiliation: State-key Laboratory of Biomembrane and Membrane Engineering, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Yeqi
authors.initials: Y
authors.lastname: Wang
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Li
authors.forename: Pengfei
authors.initials: P
authors.lastname: Xu
authors.forename: Lei
authors.initials: L
authors.lastname: Huang
authors.forename: Jingyuan
authors.initials: J
authors.lastname: Tong
authors.forename: Huizhe
authors.initials: H
authors.lastname: Huang
authors.forename: Anming
authors.initials: A
authors.lastname: Meng
mesh_terms: D020816:Amino Acid Motifs; D000091082:Angiomotins; D000818:Animals; D001808:Blood Vessels / Q000166:cytology / Q000502:physiology; D000081247:CSK Tyrosine-Protein Kinase; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement / Q000235:genetics; D016764:Cell Polarity / Q000235:genetics; D049109:Cell Proliferation; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism*; D004789:Enzyme Activation / Q000235:genetics; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018919:Neovascularization, Physiologic / Q000235:genetics; D010766:Phosphorylation / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D014443:Tyrosine / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology; D029961:Zebrafish Proteins / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D019061:src-Family Kinases
chemical_list: C508566:AMOTL2 protein, human; D000091082:Angiomotins; D002352:Carrier Proteins; D008565:Membrane Proteins; D029961:Zebrafish Proteins; C519597:amotl2a protein, zebrafish; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; C000631346:CSK protein, human; D048049:Extracellular Signal-Regulated MAP Kinases