Related Experiment Video
Updated: Jan 31, 2026
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Quantitative PCR-based Assay to Measure Sonic Hedgehog Signaling in Cellular Model of Ciliogenesis
Published on: January 31, 2025
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Unconventional Secretion of Angiogenic Sonic Hedgehog-Containing Extra-Large Extracellular Vesicles is Driven by
Shuo Wang1, Rio Imai1, Yuya Kaneko1
1Laboratory of Molecular Cell Dynamics/Cytoarchitectonics, Department of Cell Biology and Anatomy, Graduate School of Medicine The University of Tokyo Hongo Tokyo Japan.
Journal of Extracellular Biology
|January 30, 2026
Summary
Researchers discovered a new pathway involving PI3K-Rab18-GDP signaling that controls the release of extra-large extracellular vesicles (XLEVs) from stem cells. These XLEVs carry sonic hedgehog (SHH) and promote blood vessel growth.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Extra-large extracellular vesicles (XLEVs) mediate intercellular communication, but their biogenesis and regulation are unclear.
- Sonic hedgehog (SHH) signaling is crucial in development and regeneration.
Purpose of the Study:
- To elucidate the molecular mechanisms behind XLEV biogenesis and secretion.
- To understand the role of PI3K-Rab18-GDP signaling in XLEV production and function.
Main Methods:
- Utilized human mesenchymal stem cells (hMSCs) and fibroblasts.
- Employed pharmacological activators (SF1670) and inhibitors (CID1067700) targeting PI3K and Rab18.
- Investigated protein recruitment (Hsp90α, nSMase2) and vesicle localization.
Main Results:
- Identified PI3K-Rab18-GDP signaling as a key pathway for XLEV secretion in hMSCs and fibroblasts.
- Demonstrated that Rab18-GDP enrichment enhances XLEV production.
- Showed that these SHH-enriched XLEVs possess pro-angiogenic activity.
Conclusions:
- Established a novel PI3K-Rab18-GDP-dependent pathway for SHH-XLEV biogenesis and secretion.
- Linked XLEV production to SHH-associated angiogenic signaling in developmental and regenerative processes.
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