ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2026
Mechanical Cues Regulate Cargo Sorting and Export at the Golgi.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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The trial behind it
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Who cites it
4 citing papers in PubMed.
- Mechanically Regulated Secretion: How Physical Forces Instruct the Secretory Pathway and Remodel the Secretome.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Mechanical forces stimulate Golgi export.The Journal of cell biology · 2026Article
- Matrix stiffness promotes colorectal cancer progression via Golgi-dependent cholesterol synthesis.Cell death & disease · 2026Article
- Mechanical Cues Regulate Cargo Sorting and Export at the Golgi.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
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Authors and funding
22 authors.
Funding
Abstract
The secretory pathway is a sophisticated endomembrane machinery designed to transport and deliver proteins and lipids to intracellular organelles and the extracellular space. While the molecular components of the secretory pathway are well understood, less is known about their regulation, especially by mechanical cues. Here, it is reported that substrate stiffness stimulates conventional secretion. A molecular pathway is unravelled that links a mechanical cue through proto-oncogene tyrosine-protein kinase Src (Src) and focal adesion kinase (FAK) kinases to promote the trafficking of secretory proteins out of the Golgi apparatus and prevent their post-Golgi lysosomal degradation. Phosphoproteomic analysis revealed the Golgi-specific Brefeldin A resistance factor 1 (GBF1) as a key downstream mechano-responsive regulator, whose phosphorylation state orchestrates post-Golgi cargo sorting, directing proteins either toward secretion or to lysosomes. Finally, AMP-activated protein kinase (AMPK) is identified as a stiffness-dependent upstream regulator of GBF1 phosphorylation. Together, the data reveal a molecular regulatory loop in which matrix stiffness positively regulates cellular secretion via the Src-FAK-AMPK-GBF1 axis, which can have relevant medical implications in conditions like cancer and fibrosis and their treatment.
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Registered trials
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