ArticleCellular and molecular life sciences : CMLS2024
Uncovering key steps in FGF12 cellular release reveals a common mechanism for unconventional FGF protein secretion.
Article in Cellular and molecular life sciences : CMLS, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- State-Dependent FGF Signaling in Satellite Cell-Mediated Skeletal Muscle Regeneration and Pathological Remodeling.Biomolecules · 2026Review
- Beyond Ion Channels: Emerging Roles of FGF12 in Cellular Regulation and Cancer Progression.Cells · 2026Review
- FGF13 is not secreted from mouse neurons.JCI insight · 2026Article
- Transcriptome analysis of goat adipose tissue-derived mesenchymal stem cells cultured in variable oxygen conditions.Frontiers in cell and developmental biology · 2026Article
- Neuronal FGF13 Inhibits Mitochondria-Derived Damage Signals to Prevent Neuroinflammation and Neurodegeneration in a Mouse Model of Parkinson's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Specific inhibition of fibroblast growth factor receptor 1 signaling by a DNA aptamer.Molecular therapy. Nucleic acids · 2025Article
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Authors and funding
8 authors.
Funding
Abstract
FGF12 belongs to a subfamily of FGF proteins called FGF homologous factors (FHFs), which until recently were thought to be non-signaling intracellular proteins. Our recent studies have shown that although they lack a conventional signal peptide for secretion, they can reach the extracellular space, especially under stress conditions. Here, we unraveled that the long "a" isoform of FGF12 is secreted in a pathway involving the A1 subunit of Na(+)/K(+) ATPase (ATP1A1), Tec kinase and lipids such as phosphatidylinositol and phosphatidylserine. Further, we showed that the short "b" isoform of FGF12, which binds ATP1A1 and phosphatidylserine less efficiently, is not secreted from cells. We also indicated regions in the FGF12a protein sequence that are crucial for its secretion, including N-terminal fragment and specific residues, and proposed that liquid-liquid phase separation may be important in this process. Our results strongly suggest that the mechanism of this process is very similar for all unconventionally secreted FGF proteins.
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