| Speaker: |
Masanori Nakayama
Max-Planck-Institute for Molecular Biomedicine, Department of tissue morphogenesis |
| Title: |
Regulation of VEGF-induced angiogenesis by receptor endocytosis |
| Summary : | In development, tissue regeneration or certain diseases, angiogenic growth leads to the expansion of blood vessels and the lymphatic
vasculature. This involves endothelial cell proliferation as well as angiogenic sprouting, in which a subset of cells, termed tip cells,
acquires motile, invasive behaviour and extends filopodial protrusions. While it is already appreciated that angiogenesis is
triggered by tissue-derived signals, such as VEGF family growth factors, the resulting signaling processes in endothelial cells are
only partially understood.
We show that ephrin-B2, a transmembrane ligand for Eph receptor tyrosine kinases, promotes sprouting behaviour and motility in the
angiogenic endothelium. We attribute this function to a crucial role of ephrin-B2 in the VEGF signalling pathway, which we have studied in
detail for VEGFR3, the receptor for VEGF-C. In the absence of ephrin-B2, the internalisation of VEGFR3 in cultured cells and mutant mice is
defective, which compromises downstream signal transduction. Our results show that full VEGFR3 signalling requires receptor
internalisation. Ephrin-B2 is a key regulator of this step and thereby controls angiogenic and lymphangiogenic growth. |
