TY - JOUR
T1 - Interaction of cortactin and Arp2/3 complex is required for sphingosine-1-phosphate-induced endothelial cell remodeling
AU - Li, Yansong
AU - Uruno, Takehito
AU - Haudenschild, Christian
AU - Dudek, Steven M.
AU - Garcia, Joe G.N.
AU - Zhan, Xi
N1 - Funding Information:
We thank Dr. Richard C. Mulligan (Harvard Medical School, Boston, MA) for providing 293GPG packaging cells, Dr. Jian-jiang Hao and Kang Zhou for helpful discussions with this work. We also gratefully acknowledge Ms Jiali Liu and Ms Nicole Smith for technical assistance. This work was supported by NIH grant R01 HL 52753-09, R01 CA 91984-01, DOD grant DAMD 17-01-1-0125, American Heart Association grant 0040135N (XZ), and P01 HL 58064, R01 68071, and R01 50533 (JGNG). SMD received support from the Four Schools Physician-Scientist Program, NRSA HL 10403, and NIH KO8 HL70013-01.
PY - 2004/8/1
Y1 - 2004/8/1
N2 - 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.
AB - 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.
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U2 - 10.1016/j.yexcr.2004.03.023
DO - 10.1016/j.yexcr.2004.03.023
M3 - Article
C2 - 15242766
AN - SCOPUS:3042820790
SN - 0014-4827
VL - 298
SP - 107
EP - 121
JO - Experimental Cell Research
JF - Experimental Cell Research
IS - 1
ER -