Abstract
Sphingosine-1-phosphate (S1P) induces capillary formation of endothelial cells on Matrigel in accompany with actin assembly and accumulation of cortactin and Arp2/3 complex at the cell-leading edge. Suppression of cortactin expression with a cortactin antisense oligo significantly impaired S1P-induced capillary formation, migration of endothelial cells, and actin assembly at the cell periphery. Overexpression of wild-type cortactin tagged by green fluorescent protein (GFP) increased the S1P-induced tube formation and cell motility, whereas the cells overexpressing the mutant formed poorly capillary network and became less motile in response to S1P. Analysis of distribution in Triton X-100 insoluble fractions demonstrated that the cortactin mutant inhibited the association of wild-type cortactin and Arp2/3 complex with the actin-enriched complex. Furthermore, actin polymerization at and distribution of Arp2/3 complex as well as endogenous cortactin into the cell-leading edge mediated by S1P was disturbed. These data suggest that the interaction between cortactin and Arp2/3 complex plays an important role in S1P-mediated remodeling of endothelial cells.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Actin-Related Protein 2
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Actin-Related Protein 3
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Actins / biosynthesis
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Capillaries / cytology
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Capillaries / growth & development
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Capillaries / metabolism
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Cell Movement / genetics
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Cortactin
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Cytoskeletal Proteins / metabolism*
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Endothelium, Vascular / cytology
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Endothelium, Vascular / drug effects
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Endothelium, Vascular / metabolism*
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Green Fluorescent Proteins
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Humans
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Luminescent Proteins
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Lysophospholipids / metabolism*
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Lysophospholipids / pharmacology
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Macromolecular Substances
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Microfilament Proteins / antagonists & inhibitors
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Microfilament Proteins / metabolism*
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Mutation / genetics
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Neovascularization, Physiologic / genetics*
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Oligodeoxyribonucleotides, Antisense / pharmacology
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Polymers / metabolism
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Sphingosine / analogs & derivatives
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Sphingosine / metabolism*
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Sphingosine / pharmacology
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Up-Regulation / genetics
Substances
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ACTR2 protein, human
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ACTR3 protein, human
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Actin-Related Protein 2
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Actin-Related Protein 3
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Actins
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CTTN protein, human
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Cortactin
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Cytoskeletal Proteins
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Luminescent Proteins
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Lysophospholipids
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Macromolecular Substances
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Microfilament Proteins
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Oligodeoxyribonucleotides, Antisense
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Polymers
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Green Fluorescent Proteins
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sphingosine 1-phosphate
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Sphingosine