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Lipid droplets (LDs) are dynamic lipid storage organelles that can sense and respond to changes in systemic energy balance. The size and number of LDs are controlled by complex and delicate mechanisms, among which, whether and which SNARE proteins mediate LD fusion, and the mechanisms governing this process remain poorly understood. Here we identified a SNARE complex, syntaxin 18 (STX18)-SNAP23-SEC22B, that is recruited to LDs to mediate LD fusion. STX18 targets LDs with its transmembrane domain spanning the phospholipid monolayer twice. STX18-SNAP23-SEC22B complex drives LD fusion in adiposome lipid mixing and content mixing in vitro assays. CIDEC/FSP27 directly binds STX18, SEC22B, and SNAP23, and promotes the lipid mixing of SNAREs-reconstituted adiposomes by promoting LD clustering. Knockdown of STX18 in mouse liver via AAV resulted in smaller liver and reduced LD size under high-fat diet conditions. All these results demonstrate a critical role of the SNARE complex STX18-SNAP23-SEC22B in LD fusion.
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http://dx.doi.org/10.1038/s41421-023-00613-4 | DOI Listing |
PLoS Genet
September 2025
Department of Biochemistry, Indian Institute of Science, Bengaluru, Karnataka, India.
Tropomyosin is an actin-binding protein (ABP) which protects actin filaments from cofilin-mediated disassembly. Distinct tropomyosin isoforms have long been hypothesized to differentially sort to subcellular actin networks and impart distinct functionalities. Nevertheless, a mechanistic understanding of the interplay between Tpm isoforms and their functional contributions to actin dynamics has been lacking.
View Article and Find Full Text PDFACS Synth Biol
September 2025
The Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, P. R. China.
Human Bone Morphogenetic Protein-2 (hBMP-2) serves as a critical regulator in bone and cartilage formation; however, its industrial application is hindered by its inherent tendency to form inclusion bodies in prokaryotic expression systems. To address this issue, we established a recombinant hBMP-2 (rhBMP-2) expression system using the pCold II plasmid and the SHuffle T7 strain. We explored several strategies to enhance the solubility of rhBMP-2, including coexpression with molecular chaperones, vesicle-mediated secretory expression, fusion expression with synthetic intrinsically disordered proteins (SynIDPs), and fusion expression with small-molecule peptide tags.
View Article and Find Full Text PDFCancer Discov
September 2025
Moffitt Cancer Center, Tampa, FL, United States.
There is growing interest in understanding the mechanisms underlying differences in cancer incidence among species (comparative oncology). The naked mole-rat (NMR) is often referenced as "cancer-resistant" and prior studies focused on identifying mechanisms explaining this. However, efforts to assess this in vivo have been limited.
View Article and Find Full Text PDFFront Immunol
September 2025
Department of Pediatrics, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, GA, United States.
Introduction: Interferon-induced transmembrane proteins (IFITMs) inhibit the entry of diverse enveloped viruses. The spectrum of antiviral activity of IFITMs is largely determined by their subcellular localization. IFITM1 localizes to and primarily blocks viral fusion at the plasma membrane, while IFITM3 prevents viral fusion in late endosomes by accumulating in these compartments.
View Article and Find Full Text PDFMol Ther Nucleic Acids
September 2025
Department of Genetics and Biotechnology, College of Life Sciences, Kyung Hee University, Yongin-si, Gyeonggi-do 17104, Republic of Korea.
Epigenetic modulation enables precise gene regulation without altering DNA sequences. While histone acetylation has been widely utilized for gene activation, the therapeutic potential of histone methylation remains underexplored. In this study, we developed a new epigenetic activator by fusing the histone methyltransferase SETD7 to deactivated Cas9 (dCas9).
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