Ciliopathies are multisystem disorders characterized by the dysfunction of motile and/or non-motile cilia,which are microtubule-based structures protruding from the cell surface and function in cell motility and signa...Ciliopathies are multisystem disorders characterized by the dysfunction of motile and/or non-motile cilia,which are microtubule-based structures protruding from the cell surface and function in cell motility and signaling.Common clinical manifestations of ciliopathies include retinal degeneration,mental retardation,renal abnormality,obesity,and skeletal dysplasia[1,2].Fibrosis of vital organs,characterized by the extensive deposition of extracellular matrix components,represents another complication frequently observed in patients and animal models of ciliopathies[3].展开更多
Endothelial cilia are microtubule-based hair-like protrusions in the lumen of blood vessels that function as fluid mechanosensors to regulate vascular hemodynamics. However, the functions of endothelial cilia in vascu...Endothelial cilia are microtubule-based hair-like protrusions in the lumen of blood 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 intraflagellar transport 88(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 c-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.展开更多
基金supported by the National Natural Science Foundation of China(31991193,32000524,and 32100656)the National Key R&D Program of China(2021YFA1101001)。
文摘Ciliopathies are multisystem disorders characterized by the dysfunction of motile and/or non-motile cilia,which are microtubule-based structures protruding from the cell surface and function in cell motility and signaling.Common clinical manifestations of ciliopathies include retinal degeneration,mental retardation,renal abnormality,obesity,and skeletal dysplasia[1,2].Fibrosis of vital organs,characterized by the extensive deposition of extracellular matrix components,represents another complication frequently observed in patients and animal models of ciliopathies[3].
基金supported by grants from the National Key R&D Program of China(2017YFA0503502)the National Natural Science Foundation of China(31730050,31871347,and 31900502)。
文摘Endothelial cilia are microtubule-based hair-like protrusions in the lumen of blood 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 intraflagellar transport 88(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 c-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.
