Regulation of Phase Separation and Antiviral Activity of Cactin by Glycolytic Enzyme PGK Via Phosphorylation in

Overview

Journal mBio

Publisher American Society for Microbiology

Specialty Microbiology

Date 2024 Mar 6

PMID 38446061

Authors

Dongchao Chen

Chang Shi

Wen Xu

Qiqi Rong

Qingfa Wu

Affiliations

Soon will be listed here.

Abstract

Importance: Liquid-liquid phase separation (LLPS) plays an integral role in various biological processes in eukaryotic organisms. Although several studies have highlighted its crucial role in modulating immune responses in mammals, its function in immune responses in remains poorly understood. Our study investigated the role of Cactin in LLPS and its implications for immune response modulation. We identified that phosphoglycerate kinase (PGK), an essential enzyme in the glycolytic pathway, phosphorylates Cactin, facilitating its transition from a relatively stable aggregated state to a more dynamic liquid droplet phase during the phase separation process. This transformation allows Cactin to rapidly interact with other cellular components, enhancing its antiviral properties and ultimately inhibiting virus replication. These findings expand our understanding of the role of LLPS in the antiviral defense mechanism, shedding light on the intricate mechanisms underlying immune responses in .

Citing Articles

Effect of potato glycoside alkaloids on mitochondria energy metabolism of , the root rot pathogen of .

Li R, Wang B, Chen W, Zhang C, Li N, Wang Y Front Microbiol. 2025; 15:1512027.

PMID: 39943965 PMC: 11814155. DOI: 10.3389/fmicb.2024.1512027.

References

Palmer W, Medd N, Beard P, Obbard D . Isolation of a natural DNA virus of Drosophila melanogaster, and characterisation of host resistance and immune responses. PLoS Pathog. 2018; 14(6):e1007050. PMC: 6002114. DOI: 10.1371/journal.ppat.1007050. View

Costa A, Jan E, Sarnow P, Schneider D . The Imd pathway is involved in antiviral immune responses in Drosophila. PLoS One. 2009; 4(10):e7436. PMC: 2758544. DOI: 10.1371/journal.pone.0007436. View

Jousset F, Bergoin M, Revet B . Characterization of the Drosophila C virus. J Gen Virol. 1977; 34(2):269-83. DOI: 10.1099/0022-1317-34-2-269. View

Shin Y, Brangwynne C . Liquid phase condensation in cell physiology and disease. Science. 2017; 357(6357). DOI: 10.1126/science.aaf4382. View

Ogino T, Iwama M, Kinouchi J, Shibagaki Y, Tsukamoto T, Mizumoto K . Involvement of a cellular glycolytic enzyme, phosphoglycerate kinase, in Sendai virus transcription. J Biol Chem. 1999; 274(50):35999-6008. DOI: 10.1074/jbc.274.50.35999. View

Wallace M, Coffman K, Gilbert C, Ravindran S, Albery G, Abbott J . The discovery, distribution, and diversity of DNA viruses associated with in Europe. Virus Evol. 2021; 7(1):veab031. PMC: 8363768. DOI: 10.1093/ve/veab031. View

Shan Z, Tu Y, Yang Y, Liu Z, Zeng M, Xu H . Basal condensation of Numb and Pon complex via phase transition during Drosophila neuroblast asymmetric division. Nat Commun. 2018; 9(1):737. PMC: 5821850. DOI: 10.1038/s41467-018-03077-3. View

Feric M, Vaidya N, Harmon T, Mitrea D, Zhu L, Richardson T . Coexisting Liquid Phases Underlie Nucleolar Subcompartments. Cell. 2016; 165(7):1686-1697. PMC: 5127388. DOI: 10.1016/j.cell.2016.04.047. View

Zhang S, Shi L, Yang Q, Dong X, Chi S, Liu H . Molecular characterization and functional analysis of Cactin gene from Litopenaeus vannamei. Fish Shellfish Immunol. 2014; 41(2):608-17. DOI: 10.1016/j.fsi.2014.10.014. View

10.

Li P, Banjade S, Cheng H, Kim S, Chen B, Guo L . Phase transitions in the assembly of multivalent signalling proteins. Nature. 2012; 483(7389):336-40. PMC: 3343696. DOI: 10.1038/nature10879. View

11.

Patel A, Lee H, Jawerth L, Maharana S, Jahnel M, Hein M . A Liquid-to-Solid Phase Transition of the ALS Protein FUS Accelerated by Disease Mutation. Cell. 2015; 162(5):1066-77. DOI: 10.1016/j.cell.2015.07.047. View

12.

Zhang G, Wang Z, Du Z, Zhang H . mTOR Regulates Phase Separation of PGL Granules to Modulate Their Autophagic Degradation. Cell. 2018; 174(6):1492-1506.e22. DOI: 10.1016/j.cell.2018.08.006. View

13.

Jo Y, Kim Y, Park K, Seong J, Kim S, Park S . TmCactin plays an important role in Gram-negative and -positive bacterial infection by regulating expression of 7 AMP genes in Tenebrio molitor. Sci Rep. 2017; 7:46459. PMC: 5394457. DOI: 10.1038/srep46459. View

14.

Nott T, Petsalaki E, Farber P, Jervis D, Fussner E, Plochowietz A . Phase transition of a disordered nuage protein generates environmentally responsive membraneless organelles. Mol Cell. 2015; 57(5):936-947. PMC: 4352761. DOI: 10.1016/j.molcel.2015.01.013. View

15.

Ouibrahim L, Mazier M, Estevan J, Pagny G, Decroocq V, Desbiez C . Cloning of the Arabidopsis rwm1 gene for resistance to Watermelon mosaic virus points to a new function for natural virus resistance genes. Plant J. 2014; 79(5):705-16. DOI: 10.1111/tpj.12586. View

16.

Ali G, Golovkin M, Reddy A . Nuclear localization and in vivo dynamics of a plant-specific serine/arginine-rich protein. Plant J. 2003; 36(6):883-93. DOI: 10.1046/j.1365-313x.2003.01932.x. View

17.

Lin J, Ding M, Hsu Y, Tsai C . Chloroplast phosphoglycerate kinase, a gluconeogenetic enzyme, is required for efficient accumulation of Bamboo mosaic virus. Nucleic Acids Res. 2006; 35(2):424-32. PMC: 1802604. DOI: 10.1093/nar/gkl1061. View

18.

Elbaum-Garfinkle S, Kim Y, Szczepaniak K, Chen C, Eckmann C, Myong S . The disordered P granule protein LAF-1 drives phase separation into droplets with tunable viscosity and dynamics. Proc Natl Acad Sci U S A. 2015; 112(23):7189-94. PMC: 4466716. DOI: 10.1073/pnas.1504822112. View

19.

Docquier S, Tillemans V, Deltour R, Motte P . Nuclear bodies and compartmentalization of pre-mRNA splicing factors in higher plants. Chromosoma. 2004; 112(5):255-66. DOI: 10.1007/s00412-003-0271-3. View

20.

Leite T, Ferreira A, Imler J, Marques J . Distinct Roles of Hemocytes at Different Stages of Infection by Dengue and Zika Viruses in Mosquitoes. Front Immunol. 2021; 12:660873. PMC: 8169962. DOI: 10.3389/fimmu.2021.660873. View