Binding of human angiogenin inhibits actin polymerization.
Angiogenin is a potent inducer of angiogenesis, a process of blood vessel formation. It interacts with endothelial and other cells and elicits a wide range of cellular responses including migration, proliferation, and tube formation. One important target of angiogenin is endothelial cell-surface actin and their interaction might be one of essential steps in angiogenin-induced neovascularization. Based on earlier indications that angiogenin promotes actin polymerization, we studied the binding interactions between angiogenin and actin in a wide range of conditions. We showed that at subphysiological KCl concentrations, angiogenin does not promote, but instead inhibits polymerization by sequestering G-actin. At low KCl concentrations angiogenin induces formation of unstructured aggregates, which, as shown by NMR, may be caused by angiogenin's propensity to form oligomers. Binding of angiogenin to preformed F-actin does not cause depolymerization of actin filaments though it causes their stiffening. Binding of tropomyosin and angiogenin to F-actin is not competitive at concentrations sufficient for saturation of actin filaments. These observations suggest that angiogenin may cause changes in the cell cytoskeleton by inhibiting polymerization of G-actin and changing the physical properties of F-actin.
Pyatibratov
Mikhail G
MG
Institute of Protein Research, Russian Academy of Sciences, 142290 Pushchino, Moscow Region, Russia. bratov@vega.protres.ru
Tolkatchev
Dmitri
D
Plamondon
Josee
J
Xu
Ping
P
Ni
Feng
F
Kostyukova
Alla S
AS
D008841:Actin Cytoskeleton / Q000378:metabolism; D000199:Actins / Q000378:metabolism*; D000818:Animals; D002645:Chickens; D006801:Humans; D019906:Nuclear Magnetic Resonance, Biomolecular; D011485:Protein Binding; D012259:Ribonuclease, Pancreatic / Q000378:metabolism*
D000199:Actins; C046366:angiogenin; D012259:Ribonuclease, Pancreatic