KIF13B regulates angiogenesis through Golgi to plasma membrane trafficking of VEGFR2

Kaori H. Yamada, Yuki Nakajima, Melissa Geyer, Kishore K. Wary, Masuko Ushio-Fukai, Yulia Komarova, Asrar B. Malik

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Although the trafficking of newly synthesized VEGFR2 to the plasma membrane is a key determinant of angiogenesis, the molecular mechanisms of Golgi to plasma membrane trafficking are unknown. Here, we have identified a key role of the kinesin family plus-end molecular motor KIF13B in delivering VEGFR2 cargo from the Golgi to the endothelial cell surface. KIF13B is shown to interact directly with VEGFR2 on microtubules. We also observed that overexpression of truncated versions of KIF13B containing the binding domains that interact with VEGFR2 inhibited VEGF-induced capillary tube formation. KIF13B depletion prevented VEGFmediated endothelial migration, capillary tube formation and neovascularization in mice. Impairment in trafficking induced by knockdown of KIF13B shunted VEGFR2 towards the lysosomal degradation pathway. Thus, KIF13B is an essential molecular motor required for the trafficking of VEGFR2 from the Golgi, and its delivery to the endothelial cell surface mediates angiogenesis.

Original languageEnglish (US)
Pages (from-to)4518-4530
Number of pages13
JournalJournal of Cell Science
Volume127
Issue number20
DOIs
StatePublished - Jan 1 2014
Externally publishedYes

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Keywords

  • Angiogenesis
  • Kinesin
  • Signal transduction
  • Trafficking
  • VEGFR2

ASJC Scopus subject areas

  • Cell Biology

Cite this

Yamada, K. H., Nakajima, Y., Geyer, M., Wary, K. K., Ushio-Fukai, M., Komarova, Y., & Malik, A. B. (2014). KIF13B regulates angiogenesis through Golgi to plasma membrane trafficking of VEGFR2. Journal of Cell Science, 127(20), 4518-4530. https://doi.org/10.1242/jcs.156109