{"OA_place":"publisher","doi":"10.1126/sciadv.adw4124","article_processing_charge":"Yes","_id":"20370","issue":"38","external_id":{"isi":["001575751700013"],"pmid":["40971423"]},"article_type":"original","date_created":"2025-09-22T08:00:52Z","type":"journal_article","date_published":"2025-09-19T00:00:00Z","day":"19","acknowledgement":"We thank C. Cuveillier, J. Delaroche, T. Ferraro, and A. Zanchi for help with TIRF experiments, electron microscopy preparation, data analysis, and cell cultures, respectively; A. Antkowiak, C. Bosc, C. Fassier, A. Fourest-Lieuvin, and V. Brandt for helpful discussions. We acknowledge the contribution of the Photonic Imaging Center of Grenoble Institute Neuroscience which is part of the ISdV core facility and certified by the IBiSA label and ICM.Quant (RRID:SCR_026393) core facility of the Paris Brain Institute (ICM); the AniRA lentivector production facility from the CELPHEDIA Infrastructure and SFR Biosciences (UAR3444/CNRS, US8/Inserm, ENS de Lyon, UCBL); the Scientific Service Units (SSUs) of ISTA through resources provided by Scientific Computing (SciComp, A. Schloegl and S. Elefante); and the Electron Microscopy Facility (EMF, V.V. Hodirnau). The software programs used for the processing were supported by SBGrid (www.sbgrid.org). This work was supported by the Agence Nationale pour la Recherche (AXYON: ANR-18-CE16-0009-01, S.H.), Austrian Science Fund (FWF) grants (P33367, F.K.M.S.; E435, J.M.H.), ChanZuckerberg Initiative (CZI) grant (DAF2021-234754, F.K.M.S.), Hereditary Disease Foundation Research Grant (HDF 990846, M.C.), European Union (ERC: ActinID 101076260, F.K.M.S.), Fondation pour la Recherche Médicale (FRM: équipe labellisée DEQ202203014675, S.H.; PhD fellowship, FDT202001010865, R.C.), Korea Health Industry Development Institute (KHIDI) (Korea-Switzerland global research support grant: RS-2023-00266300, J.-J.S.), National Research Foundation (NRF) of Korea (Korea-Austria collaborative grant NRF-2019K1A3A1A181160, J.-J.S. and F.K.M.S.; NRF-2020R1A2B5B03001517 and RS-2024-00333346 and RS-2024-00436173, J.-J.S.; 2021R1C1C1006700, D.K.).","publisher":"American Association for the Advancement of Science","tmp":{"image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)"},"intvolume":"        11","volume":11,"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","project":[{"_id":"9B954C5C-BA93-11EA-9121-9846C619BF3A","grant_number":"P33367","name":"Structure and isoform diversity of the Arp2/3 complex"},{"_id":"7bd318a1-9f16-11ee-852c-cc9217763180","name":"In Situ Actin Structures via Hybrid Cryo-electron Microscopy","grant_number":"E435"},{"_id":"62909c6f-2b32-11ec-9570-e1476aab5308","name":"CryoMinflux-guided in-situ molecular census and structure determination","grant_number":"CZI01"},{"grant_number":"101076260","name":"A molecular atlas of Actin filament IDentities in the cell motility machinery","_id":"bd980d18-d553-11ed-ba76-ceaa645c97eb"}],"publication_status":"published","pmid":1,"file_date_updated":"2025-09-23T07:57:51Z","publication_identifier":{"issn":["2375-2548"]},"isi":1,"file":[{"access_level":"open_access","success":1,"creator":"dernst","file_id":"20372","checksum":"4e2407bdabf8d53f399eb8a20d86218e","relation":"main_file","date_created":"2025-09-23T07:57:51Z","date_updated":"2025-09-23T07:57:51Z","file_size":3599137,"content_type":"application/pdf","file_name":"2025_ScienceAdvance_Carpentier.pdf"}],"article_number":"eadw4124","publication":"Science Advances","month":"09","department":[{"_id":"FlSc"}],"has_accepted_license":"1","year":"2025","OA_type":"gold","citation":{"chicago":"Carpentier, Rémi, Jaesung Kim, Mariacristina Capizzi, Hyeongju Kim, Florian Fäßler, Jesse Hansen, Min Jeong Kim, et al. “Structure of the Huntingtin F-Actin Complex Reveals Its Role in Cytoskeleton Organization.” <i>Science Advances</i>. American Association for the Advancement of Science, 2025. <a href=\"https://doi.org/10.1126/sciadv.adw4124\">https://doi.org/10.1126/sciadv.adw4124</a>.","apa":"Carpentier, R., Kim, J., Capizzi, M., Kim, H., Fäßler, F., Hansen, J., … Humbert, S. (2025). Structure of the Huntingtin F-actin complex reveals its role in cytoskeleton organization. <i>Science Advances</i>. American Association for the Advancement of Science. <a href=\"https://doi.org/10.1126/sciadv.adw4124\">https://doi.org/10.1126/sciadv.adw4124</a>","mla":"Carpentier, Rémi, et al. “Structure of the Huntingtin F-Actin Complex Reveals Its Role in Cytoskeleton Organization.” <i>Science Advances</i>, vol. 11, no. 38, eadw4124, American Association for the Advancement of Science, 2025, doi:<a href=\"https://doi.org/10.1126/sciadv.adw4124\">10.1126/sciadv.adw4124</a>.","ieee":"R. Carpentier <i>et al.</i>, “Structure of the Huntingtin F-actin complex reveals its role in cytoskeleton organization,” <i>Science Advances</i>, vol. 11, no. 38. American Association for the Advancement of Science, 2025.","short":"R. Carpentier, J. Kim, M. Capizzi, H. Kim, F. Fäßler, J. Hansen, M.J. Kim, E. Denarier, B. Blot, M. Degennaro, S. Labou, I. Arnal, M.J. Marcaida, M.D. Peraro, D. Kim, F.K. Schur, J.-J. Song, S. Humbert, Science Advances 11 (2025).","ama":"Carpentier R, Kim J, Capizzi M, et al. Structure of the Huntingtin F-actin complex reveals its role in cytoskeleton organization. <i>Science Advances</i>. 2025;11(38). doi:<a href=\"https://doi.org/10.1126/sciadv.adw4124\">10.1126/sciadv.adw4124</a>","ista":"Carpentier R, Kim J, Capizzi M, Kim H, Fäßler F, Hansen J, Kim MJ, Denarier E, Blot B, Degennaro M, Labou S, Arnal I, Marcaida MJ, Peraro MD, Kim D, Schur FK, Song J-J, Humbert S. 2025. Structure of the Huntingtin F-actin complex reveals its role in cytoskeleton organization. Science Advances. 11(38), eadw4124."},"ddc":["570"],"scopus_import":"1","status":"public","DOAJ_listed":"1","language":[{"iso":"eng"}],"oa":1,"oa_version":"Published Version","quality_controlled":"1","author":[{"first_name":"Rémi","full_name":"Carpentier, Rémi","last_name":"Carpentier"},{"full_name":"Kim, Jaesung","last_name":"Kim","first_name":"Jaesung"},{"full_name":"Capizzi, Mariacristina","last_name":"Capizzi","first_name":"Mariacristina"},{"first_name":"Hyeongju","last_name":"Kim","full_name":"Kim, Hyeongju"},{"last_name":"Fäßler","id":"404F5528-F248-11E8-B48F-1D18A9856A87","full_name":"Fäßler, Florian","orcid":"0000-0001-7149-769X","first_name":"Florian"},{"first_name":"Jesse","orcid":"0000-0001-7967-2085","full_name":"Hansen, Jesse","last_name":"Hansen","id":"1063c618-6f9b-11ec-9123-f912fccded63"},{"first_name":"Min Jeong","last_name":"Kim","full_name":"Kim, Min Jeong"},{"full_name":"Denarier, Eric","last_name":"Denarier","first_name":"Eric"},{"full_name":"Blot, Béatrice","last_name":"Blot","first_name":"Béatrice"},{"first_name":"Marine","last_name":"Degennaro","full_name":"Degennaro, Marine"},{"full_name":"Labou, Sophia","last_name":"Labou","first_name":"Sophia"},{"full_name":"Arnal, Isabelle","last_name":"Arnal","first_name":"Isabelle"},{"first_name":"Maria J.","last_name":"Marcaida","full_name":"Marcaida, Maria J."},{"last_name":"Peraro","full_name":"Peraro, Matteo Dal","first_name":"Matteo Dal"},{"last_name":"Kim","full_name":"Kim, Doory","first_name":"Doory"},{"first_name":"Florian KM","full_name":"Schur, Florian KM","orcid":"0000-0003-4790-8078","id":"48AD8942-F248-11E8-B48F-1D18A9856A87","last_name":"Schur"},{"full_name":"Song, Ji-Joon","last_name":"Song","first_name":"Ji-Joon"},{"full_name":"Humbert, Sandrine","last_name":"Humbert","first_name":"Sandrine"}],"abstract":[{"text":"The Huntingtin protein (HTT), named for its role in Huntington’s disease, has been best understood as a scaffolding protein that promotes vesicle transport by molecular motors along microtubules. Here, we show that HTT also interacts with the actin cytoskeleton, and its loss of function disturbs the morphology and function of the axonal growth cone. We demonstrate that HTT organizes F-actin into bundles. Cryo–electron tomography (cryo-ET) and subtomogram averaging (STA) structural analyses reveal that HTT’s N-terminal HEAT and Bridge domains wrap around F-actin, while the C-terminal HEAT domain is displaced; furthermore, HTT dimerizes via the N-HEAT domain to bridge parallel actin filaments separated by ~20 nanometers. Our study provides the structural basis for understanding how HTT interacts with and organizes the actin cytoskeleton.","lang":"eng"}],"title":"Structure of the Huntingtin F-actin complex reveals its role in cytoskeleton organization","PlanS_conform":"1","date_updated":"2025-09-30T14:41:57Z","corr_author":"1"}