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Vesicle trafficking of a RhoA guanine exchange factor regulates VEGF‐driven directional migration
Author(s) -
Horowitz Arie,
Agrawal Sudesh,
Wu Chuanshen
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.9.4
Subject(s) - microbiology and biotechnology , rhoa , guanine nucleotide exchange factor , biology , signal transduction
Our objective is to test whether trafficking of the RhoA guanine exchange factor (GEF) Syx/Plekhg5 between tight junctions and the plasma membrane regulates VEGF‐driven directional migration of endothelial cells (ECs) and vessel sprouting. We found that unlike wt ECs, syx − / − ECs do not migrate in the direction of a VEGF‐A gradient, but randomly. We previously reported that syx knockdown zebrafish and syx − / − mice have similar vessel sprouting defects (Circ Res 103:710, 2008). Syx binds the PDZ adaptor protein synectin/GIPC1, which is involved in the docking of its ligand to uncoated vesicles (PNAS 103:12735, 2006). It is known that synectin − / − ECs migrate poorly in response to VEGF (Dev. Cell 10:783, 2006), indicating that synectin‐dependent trafficking is required for migration. Syx is present in tight junctions and at the leading edge of ECs migrating in response to VEGF‐A. We used endocytic markers in order to identify the trafficking pattern of Syx, and found that it collocates with Rab5 and Rab4. These observations indicate that Syx undergoes rapid recycling to the plasma membrane via early endosomes. Most of the cellular Syx population colocalized with angiomotin, a tight junction protein involved in EC migration. These results suggest that trafficking of Syx to the leading edge of cells sensing a chemoattractant gradient is involved in polarizing these cells along the direction of the chemoattractant gradient.