RhoJ defines angiogenic endothelial cell motility by integrating VEGF and Sema3E signals
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- Uemura Akiyoshi
- Division of Vascular Biology, Kobe University Graduate School of Medicine
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- Fukushima Yoko
- Division of Vascular Biology, Kobe University Graduate School of Medicine
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- Nishiyama Koichi
- Department of Physiological Chemistry and Metabolism, Graduate School of Medicine, The University of Tokyo
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- Ogura Yuichiro
- Department of Ophthalmology and Visual Science, Nagoya City University Graduate School of Medical Sciences
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- Nishikawa Shin-Ichi
- Laboratory for Stem Cell Biology, RIKEN Center for Developmental Biology
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During tissue morphogenesis, cells migrate in response to diverse extrinsic cues. For angiogenic endothelial cells (ECs), vascular endothelial growth factor (VEGF) and semaphorin 3E (Sema3E) are a pivotal attractant and repellent, respectively. However, it is still unclear how individual ECs integrate these opposite signals to determine their migratory behaviors. Here, we show that the small GTPase RhoJ is an EC-intrinsic integrator of VEGF and Sema3E signals. In its GTP-bound state, RhoJ bound to the cytoplasmic domain of PlexinD1. Upon Sema3E stimulation, RhoJ was released from PlexinD1 and directly induced cell contraction. Upon VEGF stimulation, RhoJ facilitated VEGFR2-PlexinD1 association, thereby preventing VEGFR2 degradation, prolonging downstream signal transduction events, and promoting directional EC movements. Consequently, RhoJ deficiency, even in a single allele, led to variable morphogenetic defects in retinal vascular patterning. Our results indicate that RhoJ may be a novel therapeutic target to manipulate EC motility in disease or tissue regeneration.
収録刊行物
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- Microvascular Reviews and Communications
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Microvascular Reviews and Communications 7 (1), 37-37, 2014
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詳細情報 詳細情報について
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- CRID
- 1390001205255515520
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- NII論文ID
- 130004678475
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- ISSN
- 18805906
- 21881707
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- 本文言語コード
- en
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- データソース種別
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- JaLC
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- 使用不可