PUBLICATION
Rab13-dependent trafficking of RhoA is required For directional migration and angiogenesis
- Authors
- Wu, C., Agrawal, S., Vasanji, A., Drazba, J., Sarkaria, S., Xie, J., Welsch, C.M., Anand-Apte, B., and Horowitz, A.
- ID
- ZDB-PUB-110520-2
- Date
- 2011
- Source
- The Journal of biological chemistry 286(26): 23511-20 (Journal)
- Registered Authors
- Anand-Apte, Bela, Xie, Jing
- Keywords
- cell migration, membrane trafficking, rho, trafficking, zebrafish
- MeSH Terms
-
- Animals
- Carrier Proteins/genetics
- Carrier Proteins/metabolism
- Cell Movement/physiology*
- Endothelial Cells/cytology
- Endothelial Cells/metabolism*
- GRB2 Adaptor Protein/genetics
- GRB2 Adaptor Protein/metabolism
- Guanine Nucleotide Exchange Factors/genetics
- Guanine Nucleotide Exchange Factors/metabolism
- Mice
- Mice, Knockout
- Neovascularization, Physiologic/physiology*
- Phosphorylation/physiology
- Tight Junctions/genetics
- Tight Junctions/metabolism
- Vascular Endothelial Growth Factor A/genetics
- Vascular Endothelial Growth Factor A/metabolism
- Vascular Endothelial Growth Factor Receptor-2/genetics
- Vascular Endothelial Growth Factor Receptor-2/metabolism
- Zebrafish/embryology
- Zebrafish/genetics
- rab GTP-Binding Proteins/genetics
- rab GTP-Binding Proteins/metabolism*
- rho GTP-Binding Proteins/genetics
- rho GTP-Binding Proteins/metabolism*
- PubMed
- 21543326 Full text @ J. Biol. Chem.
Citation
Wu, C., Agrawal, S., Vasanji, A., Drazba, J., Sarkaria, S., Xie, J., Welsch, C.M., Anand-Apte, B., and Horowitz, A. (2011) Rab13-dependent trafficking of RhoA is required For directional migration and angiogenesis. The Journal of biological chemistry. 286(26):23511-20.
Abstract
Angiogenesis requires concomitant remodeling of cell junctions and migration, as exemplified by recent observations of extensive
endothelial cell movement along growing blood vessels. We report that a protein complex that regulates cell junctions is required
for VEGF-driven directional migration and for angiogenesis in-vivo. The complex consists of RhoA and Syx, a RhoA guanine exchange
factor crosslinked by the Crumbs polarity protein Mupp1 to angiomotin, a
phosphatidylinositol-binding protein. The Syx-associated complex translocates to the leading edge of migrating cells by membrane
trafficking that requires the tight junction recycling GTPase Rab13. In turn, Rab13 associates with Grb2, targeting Syx and
RhoA to Tyr1175-phosphorylated VEGFR2 at the leading edge. Rab13 knockdown in zebrafish impeded sprouting of intersegmental
vessels and diminished the directionality of their tip cells. These results indicate that endothelial cell mobility in sprouting
vessels is facilitated by shuttling the same protein complex from disassembling junctions to cells2 leading edge.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping