Selective regulation of Notch ligands during angiogenesis is mediated by vimentin

Authors: Antfolk D, Sjöqvist M, Cheng F, Isoniemi K, Duran CL, Rivero-Muller A, Antila C, Niemi R, Landor S, Bouten CVC, Bayless KJ, Eriksson JE, Sahlgren CM

Journal: Proc Natl Acad Sci U S A

Year: 2017

DOI: https://doi.org/10.1073/pnas.1703057114

Abstract

Significance Angiogenesis, the formation of new blood vessels from existing ones, is essential for embryonic development and necessary for tumor growth and invasion. The Notch signaling pathway regulates angiogenesis where the two Notch ligands, Dll4 and Jagged 1, exert opposite functions on sprouting. We found that the intermediate filament vimentin balances angiogenesis by binding specifically to the proangiogenic Jagged ligands. This binding provides a force-generating mechanism on the Jagged–Notch complex to ensure efficient transendocytosis and Notch activation. The interaction between vimentin and Jagged constitutes a mechanism behind selective regulation of Notch ligands during angiogenesis. The interaction may be amendable by therapeutic intervention and can facilitate strategies targeting a variety of diseases related to Jagged deregulation.