A cilium-independent role for intraflagellar transport 88 in regulating angiogenesis

Abstract

Endothelial cilia are microtubule-based hair-like protrusions in the lumen ofblood vessels that function as fluid mechanosensors to regulate vascular hemodynamics.However, the functions of endothelial cilia in vascular development remain controversial. In this study, depletion of several key proteins responsible for ciliogenesis allows us to identify a cilium-independent role for intraflagellartransport88 (IFT88) in mammalian angiogenesis. Disruption of primary cilia by heat shock does not affect the angiogenic process. However, depletion of IFT88 significantly inhibits angiogenesis both in vitro and in vivo. IFT88 mediates angiogenesis by regulating the migration, polarization, proliferation, and oriented division of vascular endothelial cells. Further mechanistic studies demonstrate that IFT88 interacts with γ-tubulin and microtubule plus-end tracking proteins and promotes microtubule stability. Our findings indicate that IFT88 regulates angiogenesis through its actions in microtubule-based cellular processes, independent of its role in ciliogenesis.