FORMINAS: AS NUCLEADORAS DE ACTINA MULTITAREFA NA BIOLOGIA DAS CÉLULAS DENDRÍTICAS, UMA REVISÃO DA LITERATURA

Authors

  • Dr. Claudio Roberto Simon Federal University of Triângulo Mineiro (UFTM); Institute of Biological and Natural Sciences (ICBN); Department of Structural Biology (DBE) https://orcid.org/0009-0009-6567-531X
    • Dr Saulo Fernando Moreira da Silva Federal University of Triângulo Mineiro (UFTM); Institute of oncological research (IPON) https://orcid.org/0000-0001-7704-8115
      • Dra. Márcia Antoniazi Michelin Federal University of Triângulo Mineiro (UFTM); Institute of Biological and Natural Sciences (ICBN); Department of Microbiology, Immunology and Parasitology (DMIP) https://orcid.org/0000-0003-0842-8805

        DOI:

        https://doi.org/10.18554/acbiobras.v8i2.8483

        Keywords:

        Formins, Actin cytoskeleton , Immunotherapy, dendritic cells, Cell biology

        Abstract

        As células dendríticas (DCs) estão na linha de frente da defesa imunológica. São células apresentadoras de antígenos profissionais, capazes de conectar respostas imunes adaptativas e inatas, interagindo com células T e secretando citocinas. Ao realizar tais atividades, elas desempenham um papel ambíguo, seja engajando a resposta imune adequada ou iniciando doenças, e portanto, representam alvos terapêuticos importantes para imunoterapias. Esse potencial é ainda mais significativo se considerarmos a dinâmica da remodelação do citoesqueleto de actina para desempenhar tais papéis. A família de Forminas de nucleadores de actina desempenha uma das três redes reguladoras de actina. As forminas possuem papéis essenciais em praticamente todas as células eucarióticas, incluindo as DCs. Dessa forma, revisamos as funções mais proeminentes das forminas na biologia das DCs. As forminas mais proeminentes que desempenharam papéis são membros dos subtipos Diáfano e FHOS/FHOD, atuando desde o reconhecimento e captação de patógenos, ativação de células T, formação de sinapses/filopódios virais, estabilidade da migração até adesão, podendo ser consideradas como biomarcadores dos estados inativo e ativado das DCs. Esses papéis importantes nas DCs deixam importantes questões em aberto ainda sem resposta.

        References

        1. Jiménez-Cortegana C, Palomares F, Alba G, Santa-María C, de la Cruz-Merino L, Sánchez-Margalet V, López-Enríquez S. Dendritic cells: the yin and yang in disease progression. Front Immunol. 2024; (14): e1321051https://pubmed.ncbi.nlm.nih.gov/38239364/. DOI: https://doi.org/10.3389/fimmu.2023.1321051

        2. Steinman RM, Cohn ZA. Identification of a novel cell type in peripheral lymphoid organs of mice. II. Functional properties in vitro. J Exp Med. 1974; 139 (2): 380-397. https://pubmed.ncbi.nlm.nih.gov/4589990/. DOI: https://doi.org/10.1084/jem.139.2.380

        3. Collin, M, Bigley, V. Human dendritic cell subsets: an update. Immunology. 2018; 154 (1): 3-20.https://pubmed.ncbi.nlm.nih.gov/29313948/. DOI: https://doi.org/10.1111/imm.12888

        4. Benze, D, Fekete, T, Pázmándi, K. Type I Interferon Production of Plasmacytoid Dendritic Cells under Control. International Journal of Molecular Sciences, 2021; 22 (8): 4190. https://pubmed.ncbi.nlm.nih.gov/33919546/. DOI: https://doi.org/10.3390/ijms22084190

        5. Cruvinel W de M, Mesquita Júnior D, Araújo JAP, Catelan TTT, Souza AWS de, Silva NP da, et al.. Sistema imunitário: Parte I. Fundamentos da imunidade inata com ênfase nos mecanismos moleculares e celulares da resposta inflamatória. Rev Bras Reumatol, 2010; 50 (4): 434–447. https://doi.org/10.1590/S0482-50042010000400008. DOI: https://doi.org/10.1590/S0482-50042010000400008

        6. Soto, J. A. The Role of Dendritic Cells During Infections Caused by Highly Prevalent Viruses. Frontiers in Immunology, 2020; (11). https://pubmed.ncbi.nlm.nih.gov/32765522/. DOI: https://doi.org/10.3389/fimmu.2020.01513

        7. Moussion C, Delamarre L. Antigen cross-presentation by dendritic cells: A critical axis in cancer immunotherapy. Semin Immunol. 2024; (71). https://pubmed.ncbi.nlm.nih.gov/38035643/. DOI: https://doi.org/10.1016/j.smim.2023.101848

        8. Domingues, B. A atuação das células dendríticas na manutenção da imunidade. Revista Multidisciplinar em Saúde, 2023; 4 (2). https://ime.events/conbrai2023/pdf/14357. DOI: https://doi.org/10.51161/iii-conbrai/14357

        9. Jamal, ME, Shibli, F. Dendritic cell and co-stimulatory molecule targeted therapy for autoimmune diseases: a review of the newly implemented strategies. Exploratory Immunology, 2024; (4): 189–210. https://doi.org/10.37349/ei.2024.00136. DOI: https://doi.org/10.37349/ei.2024.00136

        10. Conti, BJ, Santiago, KB, Sforcin, JM. Células dendríticas: mini-revisão. Biosaúde, 2014; 16 (1): 28-34. https://www.uel.br/revistas/uel/index.php/biosaude/article/view/24351/0.

        11. Brooks JW, Tillu V, Eckert J, Verma S, Collins BM, Parton RG, Yap AS. Caveola mechanotransduction reinforces the cortical cytoskeleton to promote epithelial resilience. Mol Biol Cell. 2023; 34 (12) https://pubmed.ncbi.nlm.nih.gov/37672337/. DOI: https://doi.org/10.1091/mbc.E23-05-0163

        12. Wang H, Hu J, Yi K, Ma Z, Song X, Lee Y, Kalab P, Bershadsky AD, Miao Y, Li R. Dual control of formin-nucleated actin assembly by the chromatin and ER in mouse oocytes. Curr Biol. 2022; 32 (18): 4013-4024. https://pubmed.ncbi.nlm.nih.gov/35981539/. DOI: https://doi.org/10.1016/j.cub.2022.07.058

        13. Parisis N, Krasinska L, Harker B, Urbach S, Rossignol M, Camasses A, Dewar J, Morin N, Fisher D. Initiation of DNA replication requires actin dynamics and formin activity. EMBO J. 2017; 36 (21): 3212-3231. https://pubmed.ncbi.nlm.nih.gov/28982779/. DOI: https://doi.org/10.15252/embj.201796585

        14. Krause M, Dent EW, Bear JE, Loureiro JJ, Gertler FB. Ena/VASP proteins: regulators of the actin cytoskeleton and cell migration. Annu Rev Cell Dev Biol. 2003; 19: 541-564. https://pubmed.ncbi.nlm.nih.gov/14570581/. DOI: https://doi.org/10.1146/annurev.cellbio.19.050103.103356

        15. Pruyne D. Revisiting the Phylogeny of the Animal Formins: Two New Subtypes, Relationships with Multiple Wing Hairs Proteins, and a Lost Human Formin. PLoS One. 2016; 11 (10): e0164067. https://pubmed.ncbi.nlm.nih.gov/27695129/. DOI: https://doi.org/10.1371/journal.pone.0164067

        16. Valencia DA, Quinlan ME. Formins. Curr Biol. 2021; 31 (10): R517-R522. https://pubmed.ncbi.nlm.nih.gov/34033783/. DOI: https://doi.org/10.1016/j.cub.2021.02.047

        17. Gutiérrez-Martínez E, Benet Garrabé S, Mateos N, Erkizia I, Nieto-Garai JA, Lorizate M, Borgman KJE, Manzo C, Campelo F, Izquierdo-Useros N, Martinez-Picado J, Garcia-Parajo MF. Actin-regulated Siglec-1 nanoclustering influences HIV-1 capture and virus-containing compartment formation in dendritic cells. Elife. 2023; 20 (12): e78836. https://pubmed.ncbi.nlm.nih.gov/36940134/. DOI: https://doi.org/10.7554/eLife.78836

        18. Vargas P, Barbier L, Sáez PJ, Piel M.. Mechanisms for fast cell migration in complex environments. Current Opinion in Cell Biology 2017; 48:72–78. https://pubmed.ncbi.nlm.nih.gov/28641118/. DOI: https://doi.org/10.1016/j.ceb.2017.04.007

        19. Descamps D, Evnouchidou I, Caillens V, Drajac C, Riffault S, van Endert P, Saveanu L. The Role of Insulin Regulated Aminopeptidase in Endocytic Trafficking and Receptor Signaling in Immune Cells. Front Mol Biosci. 2020; (7): e583556. https://pubmed.ncbi.nlm.nih.gov/33195428/. DOI: https://doi.org/10.3389/fmolb.2020.583556

        20. Tojo H, Kaieda I, Hattori H, Katayama N, Yoshimura K, Kakimoto S, et al. The Formin family protein, formin homolog overexpressed in spleen, interacts with the insulin-responsive aminopeptidase and profilin IIa. Mol. Endocrinol. 2003; 17: 1216–1229. https://academic.oup.com/mend/article/17/7/1216/275643. DOI: https://doi.org/10.1210/me.2003-0056

        21. Babdor J, Descamps D, Adiko, AC, Tohmé M, Maschalidi S, Evnouchidou I, et al. IRAP+ endosomes restrict TLR9 activation and signaling. Nat. Immunol. 2017; 18: 509–518.https://pubmed.ncbi.nlm.nih.gov/28319098/. DOI: https://doi.org/10.1038/ni.3711

        22. Fernandez-Borja M, Janssen L, Verwoerd D, Hordijk P, Neefjes J. . RhoB regulates endosome transport by promoting actin assembly on endosomal membranes through Dia1. J. Cell. Sci. 2005; 118: 2661–2670. https://pubmed.ncbi.nlm.nih.gov/15944396/. DOI: https://doi.org/10.1242/jcs.02384

        23. Weimershaus M, Mauvais FX, Saveanu L, Adiko C, Babdor J, Abramova A, et al. Innate immune signals induce anterograde endosome transport promoting MHC class I cross-presentation. Cell. Rep. 2018; 24: 3568–3581. https://pubmed.ncbi.nlm.nih.gov/30257216/. DOI: https://doi.org/10.1016/j.celrep.2018.08.041

        24. Rezaei Z, Tahmasebi A, Pourabbas B. Using meta-analysis and machine learning to investigate the transcriptional response of immune cells to Leishmania infection. PLoS Negl Trop Dis. 2024; 18 (1): e0011892. https://pubmed.ncbi.nlm.nih.gov/38190401/. DOI: https://doi.org/10.1371/journal.pntd.0011892

        25. Kushwaha R, Seth A, Jijumon A, Reshmi P, Dileep D, Datta R, et al.. Leishmania major formins are cytosolic actin bundlers play an important role in cell physiology. bioRxiv. 2021; 4 (12): .https://www.biorxiv.org/lookup/doi/10.1101/2021.04.12.439584.

        26. Shrivastava A, Prasad A, Kuzontkoski PM, Yu J, Groopman JE. Slit2N Inhibits Transmission of HIV-1 from Dendritic Cells to T-cells by Modulating Novel Cytoskeletal Elements. Sci Rep. 2015; 5: https://pubmed.ncbi.nlm.nih.gov/26582347/. DOI: https://doi.org/10.1038/srep16833

        27. Aggarwal A, Iemma TL, Shih, I, Newsome, TP, McAllery, S, Cunningham, AL, Turville, SG. Mobilization of HIV spread by diaphanous 2 dependent filopodia in infected dendritic cells. PLoS Pathog 2012; 8: e1002762, https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1002762.

        28. Higashi T, Ikeda T, Murakami T, Shirakawa R, Kawato M, Okawa K, Furuse M, Kimura T, Kita T, Horiuchi H. Flightless-I (Fli-I) regulates the actin assembly activity of diaphanous-related formins (DRFs) Daam1 and mDia1 in cooperation with active Rho GTPase. J Biol Chem. 2010; 285 (21):16231-16238, https://pubmed.ncbi.nlm.nih.gov/20223827/. DOI: https://doi.org/10.1074/jbc.M109.079236

        29. Ostrowski PP, Grinstein S, Freeman SA. Diffusion Barriers, Mechanical Forces, and the Biophysics of Phagocytosis. Dev Cell. 2016; 38 (2): 135-146. https://pubmed.ncbi.nlm.nih.gov/27459066/. DOI: https://doi.org/10.1016/j.devcel.2016.06.023

        30. Lomakin AJ, Lee KC, Han SJ, Bui DA, Davidson M, Mogilner A, Danuser G. Competition for actin between two distinct F-actin networks defines a bistable switch for cell polarization. Nat Cell Biol. 2015; 17 (11): 1435-1445. https://pubmed.ncbi.nlm.nih.gov/26414403/. DOI: https://doi.org/10.1038/ncb3246

        31. Vargas P, Maiuri P, Bretou M, Sáez PJ, Pierobon P, Maurin M, Chabaud M, Lankar D, Obino D, Terriac E, Raab M, Thiam HR, Brocker T, Kitchen-Goosen SM, Alberts AS, Sunareni P, Xia S, Li R, Voituriez R, Piel M, Lennon-Duménil AM. Innate control of actin nucleation determines two distinct migration behaviors in dendritic cells. Nat Cell Biol. 2016; 18 (1): 43-53. https://pubmed.ncbi.nlm.nih.gov/26641718/. DOI: https://doi.org/10.1038/ncb3284

        32. Tanizaki H, Egawa G, Inaba K, Honda T, Nakajima S, Moniaga CS, Otsuka A, Ishizaki T, Tomura M, Watanabe T, Miyachi Y, Narumiya S, Okada T, Kabashima K. Rho-mDia1 pathway is required for adhesion, migration, and T-cell stimulation in dendritic cells. Blood. 2010; 116 (26): 5875-5884. https://pubmed.ncbi.nlm.nih.gov/20881208/. DOI: https://doi.org/10.1182/blood-2010-01-264150

        33. Aggarwal A, Iemma TL, Shih I, Newsome TP, McAllery S, Cunningham AL, Turville SG. Mobilization of HIV spread by diaphanous 2 dependent filopodia in infected dendritic cells. PLoS Pathog. 2012; 8 (6): e1002762. https://pubmed.ncbi.nlm.nih.gov/22685410/. DOI: https://doi.org/10.1371/journal.ppat.1002762

        34. Visweswaran SP, Nayab H, Hoffmann L, Gil M, Liu F, Kühne R, Maritzen T. Ena/VASP proteins at the crossroads of actin nucleation pathways in dendritic cell migration. Front Cell Dev Biol. 2022; 10: e1008898. https://pubmed.ncbi.nlm.nih.gov/36274843/. DOI: https://doi.org/10.3389/fcell.2022.1008898

        35. Bruhmann, S, Ushakov, D S, Winterhoff, M, Dickinson, RB, Curth, U, Faix, J. Distinct VASP tetramers synergize in the processive elongation of individual actin filaments from clustered arrays. Proc. Natl. Acad. Sci. U. S. A. 2017; 114 (29): E5815–E5824. https://pubmed.ncbi.nlm.nih.gov/28667124/. DOI: https://doi.org/10.1073/pnas.1703145114

        36. Chen XJ, Squarr AJ, Stephan R, Chen B, Higgins TE, Barry, D. J., et al. Ena/VASP proteins cooperate with the WAVE complex to regulate the actin cytoskeleton. Dev. Cell. 2014; 30 (5): 569–584. https://pubmed.ncbi.nlm.nih.gov/25203209/. DOI: https://doi.org/10.1016/j.devcel.2014.08.001

        37. Naj X, Hoffmann AK, Himmel M, Linder S. The formins FMNL1 and mDia1 regulate coiling phagocytosis of Borrelia burgdorferi by primary human macrophages. Infect Immun. 2013; 81 (5): 1683-1695. https://pubmed.ncbi.nlm.nih.gov/23460512/. DOI: https://doi.org/10.1128/IAI.01411-12

        38. Miller MR, Blystone SD. Human Macrophages Utilize the Podosome Formin FMNL1 for Adhesion and Migration. Cellbio (Irvine, Calif). 2015; 4 (1): 1-11. https://pubmed.ncbi.nlm.nih.gov/26942206/. DOI: https://doi.org/10.4236/cellbio.2015.41001

        39. Williams SK, Weiner ZP, Gilmore RD. Human neuroglial cells internalize Borrelia burgdorferi by coiling phagocytosis mediated by Daam1. PLoS One. 2018; 13 (5): e0197413. https://pubmed.ncbi.nlm.nih.gov/29746581/. DOI: https://doi.org/10.1371/journal.pone.0197413

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        Published

        2025-10-31

        Issue

        Vol. 8 No. 2 (2025)

        Section

        Revisão da Literatura

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        How to Cite

        1.
        Simon CR, da Silva SFM, Michelin MA. FORMINAS: AS NUCLEADORAS DE ACTINA MULTITAREFA NA BIOLOGIA DAS CÉLULAS DENDRÍTICAS, UMA REVISÃO DA LITERATURA. Acta Biol. Bras. [Internet]. 2025 Oct. 31 [cited 2026 Apr. 6];8(2):26-51. Available from: https://seer.uftm.edu.br/revistaeletronica/index.php/acbioabras/article/view/8483