ArticleAngiogenesis2021
The endosomal RIN2/Rab5C machinery prevents VEGFR2 degradation to control gene expression and tip cell identity during angiogenesis.
Article in Angiogenesis, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 50 citations in OpenAlex.
- RAB5c orchestrates LC3-associated phagocytosis to promote microbicidal function of macrophages.Science advances · 2026Article
- RAB5C Increases Endothelial Release of VWF by Regulating Vesicle Trafficking.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- New perspectives on fetal and neonatal alloimmune thrombocytopenia for obstetricians.Frontiers in immunology · 2026Review
- Bioinformatic Approach to Identify PotentialInternational journal of molecular sciences · 2025Article
- Activin A Prevents Hyperresponsiveness to Vascular Endothelial Growth Factor in Pathologic Blood Vessels by Perturbing the Trafficking of Activated Vascular Endothelial Growth Factor Receptor 2.The American journal of pathology · 2025Article
- Kindlin-3 Promotes Angiogenesis via Notch Signalling and Is Crucial for Functional Recovery Postmyocardial Infarction.Journal of cellular and molecular medicine · 2025Article
- Components of the Endosome-Lysosome Vesicular Machinery as Drivers of the Metastatic Cascade in Prostate Cancer.Cancers · 2024Review
- Angiogenesis is limited by LIC1-mediated lysosomal trafficking.Angiogenesis · 2024Article
- Review
- Succinate-induced macrophage polarization and RBP4 secretion promote vascular sprouting in ocular neovascularization.Journal of neuroinflammation · 2023Article
- Matrix Metalloproteinase 9/microRNA-145 Ratio: Bridging Genomic and Immunological Variabilities in Thyroid Cancer.Biomedicines · 2023Article
- Macrocephaly and developmental delay caused by missense variants in RAB5C.Human molecular genetics · 2023Article
- Targeting FSCN1 with an oral small-molecule inhibitor for treating ocular neovascularization.Journal of translational medicine · 2023Article
- Integrin-Dependent Cell-Matrix Adhesion in Endothelial Health and Disease.Circulation research · 2023Review
- Rab35 governs apicobasal polarity through regulation of actin dynamics during sprouting angiogenesis.Nature communications · 2022Article
- Article
- Quantitative Assessment of the Apical and Basolateral Membrane Expression of VEGFR2 and NRP2 in VEGF-A-stimulated Cultured Human Umbilical Vein Endothelial Cells.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2022Article
- Trafficking in blood vessel development.Angiogenesis · 2022Review
- Small GTPases and Their Regulators: A Leading Road toward Blood Vessel Development in Zebrafish.International journal of molecular sciences · 2022Review
- HSPA12A Stimulates p38/ERK-AP-1 Signaling to Promote Angiogenesis and Is Required for Functional Recovery Postmyocardial Infarction.Oxidative medicine and cellular longevity · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 6 institutions in 3 countries.
Funding
Abstract
Sprouting angiogenesis is key to many pathophysiological conditions, and is strongly regulated by vascular endothelial growth factor (VEGF) signaling through VEGF receptor 2 (VEGFR2). Here we report that the early endosomal GTPase Rab5C and its activator RIN2 prevent lysosomal routing and degradation of VEGF-bound, internalized VEGFR2 in human endothelial cells. Stabilization of endosomal VEGFR2 levels by RIN2/Rab5C is crucial for VEGF signaling through the ERK and PI3-K pathways, the expression of immediate VEGF target genes, as well as specification of angiogenic 'tip' and 'stalk' cell phenotypes and cell sprouting. Using overexpression of Rab mutants, knockdown and CRISPR/Cas9-mediated gene editing, and live-cell imaging in zebrafish, we further show that endosomal stabilization of VEGFR2 levels is required for developmental angiogenesis in vivo. In contrast, the premature degradation of internalized VEGFR2 disrupts VEGF signaling, gene expression, and tip cell formation and migration. Thus, an endosomal feedforward mechanism maintains receptor signaling by preventing lysosomal degradation, which is directly linked to the induction of target genes and cell fate in collectively migrating cells during morphogenesis.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.