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Updated: Aug 6, 2025
09:04
A Simple Bioassay for the Evaluation of Vascular Endothelial Growth Factors
Published on: March 15, 2016
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KIF13B mediates VEGFR2 recycling to modulate vascular permeability.
Hyun-Dong Cho1,2, Nguyễn Thị Thanh Nhàn1, Christopher Zhou1
1Department of Pharmacology and Regenerative Medicine, University of Illinois College of Medicine, Chicago, IL, 60612, USA.
Cellular and Molecular Life Sciences : CMLS
|March 17, 2023
Summary
Kinesin-3 protein KIF13B recycles internalized VEGFR2, regulating blood vessel permeability. Inhibiting KIF13B reduces vascular leakage in wet age-related macular degeneration, offering a potential therapeutic strategy.
Area of Science:
- Cell Biology
- Molecular Biology
- Vascular Biology
Background:
- Vascular endothelial growth factor-A (VEGF-A) signaling drives angiogenesis and vascular leakage in disease.
- Kinesin-3 family protein KIF13B is crucial for cell surface trafficking of VEGFR2, a key mediator of VEGF-A signaling.
- The exact mechanisms by which KIF13B influences VEGF-induced signaling and endothelial permeability remain unclear.
Purpose of the Study:
- To elucidate the role of KIF13B in regulating VEGFR2 trafficking and its impact on endothelial permeability.
- To investigate the molecular mechanisms linking KIF13B, VEGFR2 recycling, and VEGF-induced signaling pathways.
- To assess the therapeutic potential of targeting KIF13B-mediated VEGFR2 trafficking in a model of wet age-related macular degeneration.
Main Methods:
- Investigated KIF13B's role in VEGFR2 internalization and recycling using cell-based assays.
- Utilized immunofluorescence microscopy to track VEGFR2 localization and association with endosomal markers (Rab5, Rab11).
- Assessed the impact of KIF13B inhibition on VEGFR2 phosphorylation, downstream signaling (SRC, VE-cadherin), and endothelial permeability in vitro and in vivo.
Main Results:
- KIF13B mediates the recycling of internalized, phosphorylated VEGFR2 via Rab11-positive vesicles, regulating endothelial permeability.
- Inhibition of KIF13B attenuated key phosphorylation events (VEGFR2 Y951, SRC Y416, VE-cadherin Y685) essential for permeability.
- Disruption of KIF13B function led to VEGFR2 lysosomal degradation and reduced vascular leakage in a wet AMD animal model.
Conclusions:
- VEGFR2 recycling, regulated by KIF13B, is fundamental to controlling vascular permeability.
- KIF13B plays a critical role in maintaining VEGFR2 surface expression and preventing its degradation.
- Targeting KIF13B-mediated VEGFR2 trafficking presents a promising therapeutic avenue for mitigating pathological vascular leakage in inflammatory diseases like wet AMD.
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