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Cryo-ET suggests tubulin chaperones form a subset of microtubule lumenal particles with a role in maintaining neuronal microtubules

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dc.contributor.authorSaikat, Charaborty
dc.contributor.authorAntonio, Martinez-Sanchez
dc.contributor.authorFlorian, Beck
dc.contributor.authorMauricio, Toro-Nahuelpan
dc.contributor.authorIn-Young, Hwang
dc.contributor.authorKyung-Min, Noh
dc.contributor.authorWolfgang, Baumeister
dc.contributor.authorJulia, Mahamid
dc.contributor.departmentIngeniería de la Información y las Comunicaciones
dc.date.accessioned2025-02-05T09:43:36Z
dc.date.available2025-02-05T09:43:36Z
dc.description.abstractThe functional architecture of the long-lived neuronal microtubule (MT) cytoskeleton is maintained by various MT-associated proteins (MAPs), most of which are known to bind to the MT outer surface. However, electron microscopy (EM) has long ago revealed the presence of particles inside the lumens of neuronal MTs, of yet unknown identity and function. Here, we use cryogenic electron tomography (cryo-ET) to analyze the three-dimensional (3D) organization and structures of MT lumenal particles in primary hippocampal neurons, human induced pluripotent stem cell–derived neurons, and pluripotent and differentiated P19 cells. We obtain in situ density maps of several lumenal particles from the respective cells and detect common structural features underscoring their potential overarching functions. Mass spectrometry-based proteomics combined with structural modeling suggest that a subset of lumenal particles could be tubulin-binding cofactors (TBCs) bound to tubulin monomers. A different subset of smaller particles, which remains unidentified, exhibits densities that bridge across the MT protofilaments. We show that increased lumenal particle concentration within MTs is concomitant with neuronal differentiation and correlates with higher MT curvatures. Enrichment of lumenal particles around MT lattice defects and at freshly polymerized MT open-ends suggests a MT protective role. Together with the identified structural resemblance of a subset of particles to TBCs, these results hint at a role in local tubulin proteostasis for the maintenance of long-lived neuronal MTs.es
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dc.identifier.citationProceedings of the National Academy of Sciences of the United States of America (PNAS)
dc.identifier.doihttps://doi.org/10.1073/pnas.2404017121
dc.identifier.urihttp://hdl.handle.net/10201/150088
dc.languageenges
dc.relationA.M.-S. was supported by the Deutsche Forschungsgemeinschaft under Germany’s Excellence Strategy—EXC 2067/1-390729940, Ramon y Cajal program RYC2021-032626-I of the Spanish State Research Agency (AEI) and Attract-RYC 2023 program of the University of Murcia. M.T-N and I.H were supported by a fellowship from the EMBL Interdisciplinary Postdoctoral Program (EI3POD) under Marie Sklodowska-Curie Actions COFUND. W.B. acknowledges support from the Center for Integrated Protein Science, Munich. J.M. acknowledges the EMBL cryo-EM platform and funding from the EMBL. Open access funding provided by the Max Planck Society.es
dc.rightsinfo:eu-repo/semantics/openAccesses
dc.rightsAtribución 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.titleCryo-ET suggests tubulin chaperones form a subset of microtubule lumenal particles with a role in maintaining neuronal microtubuleses
dc.typeinfo:eu-repo/semantics/articlees
dspace.entity.typePublicationes
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