The development of a seedling into a photosynthetically active plant is a crucial process. Despite its importance, we do not fully understand the regulatory mechanisms behind the establishment of ...

AMPK is an energy sensor that regulates cellular functions in response to changes in energy availability. However, whether AMPK activity is spatially regulated, and the implications for cell function,...

The authors developed a new system using brefeldin A and its resistant version of GBF1 knocked in, which can manipulate cargo transport from the trans-Golgi network to recycling endosomes. Details are...

Read the full paper: Broad-spectrum antiviral activity of antisense oligonucleotides targeting GBF1 against SARS-CoV-2 and influenza viruses

The authors developed a new system using brefeldin A and its resistant version of GBF1 knocked in, which can manipulate cargo transport from the trans-Golgi network to recycling endosomes. Details are...

2026.03.05 大阪大学 プレスリリース 【研究成果のポイント】インフルエンザウイルスと新型コロナウイルスに共通して増殖に必要な宿主因子※1GBF1※2を同定GBF1...

Golgi homeostasis require the activation of Arf GTPases by the guanine-nucleotide exchange factor GBF1, whose recruitment to the Golgi represents a rate limiting step in the process. GBF1 contains a c...

A pathway is identified linking extracellular matrix stiffness to secretion via Src–FAK–AMPK–GBF1 signaling. Golgi-localized GBF1 acts as a mechanotransducer whose phosphorylation controls post-Golgi cargo sorting toward secretion or lysosomal degradation. This stiffness-dependent mechanism shapes the secretome and, when dysregulated, may drive diseases like cancer and fibrosis, highlighting GBF1 as a potential therapeutic target. 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.