{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T11:20:35Z","timestamp":1791285635785,"version":"4.1.0"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,11,18]],"date-time":"2021-11-18T00:00:00Z","timestamp":1637193600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004794","name":"Centre National de la Recherche Scientifique","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004794","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008222","name":"Universit\u00e9 de Montpellier","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008222","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004097","name":"Fondation ARC pour la Recherche sur le Cancer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004097","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002915","name":"Fondation pour la Recherche M\u00e9dicale","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002915","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004099","name":"Ligue Contre le Cancer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004099","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>Osteoclasts are bone resorbing cells that participate in the maintenance of bone health. Pathological increase in osteoclast activity causes bone loss, eventually resulting in osteoporosis. Actin cytoskeleton of osteoclasts organizes into a belt of podosomes, which sustains the bone resorption apparatus and is maintained by microtubules. Better understanding of the molecular mechanisms regulating osteoclast cytoskeleton is key to understand the mechanisms of bone resorption, in particular to propose new strategies against osteoporosis. We reported recently that \u03b2-tubulin isotype TUBB6 is key for cytoskeleton organization in osteoclasts and for bone resorption. Here, using an osteoclast model CRISPR\/Cas9 KO for Tubb6, we show that TUBB6 controls both microtubule and actin dynamics in osteoclasts. Osteoclasts KO for Tubb6 have reduced microtubule growth speed with longer growth life time, higher levels of acetylation, and smaller EB1-caps. On the other hand, lack of TUBB6 increases podosome life time while the belt of podosomes is destabilized. Finally, we performed proteomic analyses of osteoclast microtubule-associated protein enriched fractions. This highlighted ARHGAP10 as a new microtubule-associated protein, which binding to microtubules appears to be negatively regulated by TUBB6. ARHGAP10 is a negative regulator of CDC42 activity, which participates in actin organization in osteoclasts. Our results suggest that TUBB6 plays a key role in the control of microtubule and actin cytoskeleton dynamics in osteoclasts. Moreover, by controlling ARHGAP10 association with microtubules, TUBB6 may participate in the local control of CDC42 activity to ensure efficient bone resorption.<\/jats:p>","DOI":"10.3389\/fcell.2021.778887","type":"journal-article","created":{"date-parts":[[2021,11,18]],"date-time":"2021-11-18T04:52:25Z","timestamp":1637211145000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":26,"title":["The Beta-Tubulin Isotype TUBB6 Controls Microtubule and Actin Dynamics in Osteoclasts"],"prefix":"10.3389","volume":"9","author":[{"given":"Justine","family":"Maurin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Morel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Gu\u00e9rit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julien","family":"Cau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serge","family":"Urbach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Blangy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume","family":"Bompard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,11,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"3123","DOI":"10.1091\/mbc.E04-01-0060","article-title":"A ubiquitous beta-tubulin disrupts microtubule assembly and inhibits cell proliferation.","volume":"15","author":"Bhattacharya","year":"2004","journal-title":"Mol. Biol. Cell"},{"key":"B2","doi-asserted-by":"publisher","first-page":"13023","DOI":"10.1074\/jbc.M900167200","article-title":"Molecular basis for class V beta-tubulin effects on microtubule assembly and paclitaxel resistance.","volume":"284","author":"Bhattacharya","year":"2009","journal-title":"J. Biol. Chem."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1025","DOI":"10.1091\/mbc.E10-10-0822","article-title":"Class V \u03b2-tubulin alters dynamic instability and stimulates microtubule detachment from centrosomes.","volume":"22","author":"Bhattacharya","year":"2011","journal-title":"Mol. Biol. Cell"},{"key":"B4","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1016\/j.ejcb.2014.07.006","article-title":"Microtubule acetylation regulates dynamics of KIF1C-powered vesicles and contact of microtubule plus ends with podosomes.","volume":"93","author":"Bhuwania","year":"2014","journal-title":"Eur. J. Cell Biol."},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.244798","article-title":"The osteoclast cytoskeleton - current understanding and therapeutic perspectives for osteoporosis.","volume":"133","author":"Blangy","year":"2020","journal-title":"J. Cell Sci."},{"key":"B6","doi-asserted-by":"publisher","first-page":"2866","DOI":"10.1016\/j.celrep.2018.10.095","article-title":"CSAP acts as a regulator of TTLL-mediated microtubule glutamylation.","volume":"25","author":"Bompard","year":"2018","journal-title":"Cell Rep."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1391","DOI":"10.1016\/j.biocel.2008.12.007","article-title":"The Rho GTPase Wrch1 regulates osteoclast precursor adhesion and migration.","volume":"41","author":"Brazier","year":"2009","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-02904-x","article-title":"Lymphocyte-specific protein 1 regulates mechanosensory oscillation of podosomes and actin isoform-based actomyosin symmetry breaking.","volume":"9","author":"Cervero","year":"2018","journal-title":"Nat. Commun."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1367","DOI":"10.1038\/nbt.1511","article-title":"MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification.","volume":"26","author":"Cox","year":"2008","journal-title":"Nat. Biotechnol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"2901","DOI":"10.1242\/jcs.02425","article-title":"A novel Rho-mDia2-HDAC6 pathway controls podosome patterning through microtubule acetylation in osteoclasts.","volume":"118","author":"Destaing","year":"2005","journal-title":"J. Cell Sci."},{"key":"B11","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1038\/s41580-018-0067-1","article-title":"Actin-microtubule crosstalk in cell biology.","volume":"20","author":"Dogterom","year":"2019","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"B12","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1083\/jcb.200701148","article-title":"Defective microtubule-dependent podosome organization in osteoclasts leads to increased bone density in Pyk2(-\/-) mice.","volume":"178","author":"Gil-Henn","year":"2007","journal-title":"J. Cell Biol."},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.239772","article-title":"Primary myeloid cell proteomics and transcriptomics: importance of \u03b2-tubulin isotypes for osteoclast function.","volume":"133","author":"Gu\u00e9rit","year":"2020","journal-title":"J. Cell Sci."},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1111\/boc.201900014","article-title":"Dock5 is a new regulator of microtubule dynamic instability in osteoclasts.","volume":"111","author":"Guimbal","year":"2019","journal-title":"Biol. Cell"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1981","DOI":"10.1172\/JCI39650","article-title":"Cdc42 regulates bone modeling and remodeling in mice by modulating RANKL\/M-CSF signaling and osteoclast polarization.","volume":"120","author":"Ito","year":"2010","journal-title":"J. Clin. Invest."},{"key":"B16","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1038\/s41580-020-0214-3","article-title":"The tubulin code and its role in controlling microtubule properties and functions.","volume":"21","author":"Janke","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1016\/j.humpath.2018.01.009","article-title":"The absence of class III \u03b2-tubulin is predictive of a favorable response to nab-paclitaxel and gemcitabine in patients with unresectable pancreatic ductal adenocarcinoma.","volume":"74","author":"Kato","year":"2018","journal-title":"Hum. Pathol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"898","DOI":"10.1016\/S2213-8587(17)30188-2","article-title":"Osteoporosis treatment: recent developments and ongoing challenges.","volume":"5","author":"Khosla","year":"2017","journal-title":"Lancet Diabetes Endocrinol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"53653","DOI":"10.1074\/jbc.M410530200","article-title":"Identification and Characterization of PS-GAP as a novel regulator of caspase-activated PAK-2.","volume":"279","author":"Koeppel","year":"2004","journal-title":"J. Biol. Chem."},{"key":"B20","doi-asserted-by":"crossref","first-page":"2811","DOI":"10.1091\/mbc.e05-11-1010","article-title":"The kinesin KIF1C and microtubule plus ends regulate podosome dynamics in macrophages.","volume":"17","author":"Kopp","year":"2006","journal-title":"Mol. Biol. Cell"},{"key":"B21","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1002\/cm.20436","article-title":"Tumoral and tissue-specific expression of the major human beta-tubulin isotypes.","volume":"67","author":"Leandro-Garc\u00eda","year":"2010","journal-title":"Cytoskeleton"},{"key":"B22","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method.","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"B23","doi-asserted-by":"publisher","first-page":"568","DOI":"10.1016\/j.ejcb.2018.10.002","article-title":"Combined strategy of siRNA and osteoclast actin cytoskeleton automated imaging to identify novel regulators of bone resorption shows a non-mitotic function for anillin.","volume":"97","author":"Maurin","year":"2018","journal-title":"Eur. J. Cell Biol."},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0087402","article-title":"The RhoGAP activity of myosin IXB is critical for osteoclast podosome patterning, motility, and resorptive capacity.","volume":"9","author":"McMichael","year":"2014","journal-title":"PLoS One"},{"key":"B25","doi-asserted-by":"publisher","first-page":"13680","DOI":"10.1021\/acs.jmedchem.0c01201","article-title":"Novel 2,7-diazaspiro[4,4]nonane derivatives to inhibit mouse and human osteoclast activities and prevent bone loss in ovariectomized mice without affecting bone formation.","volume":"63","author":"Mounier","year":"2020","journal-title":"J. Med. Chem."},{"key":"B26","doi-asserted-by":"publisher","first-page":"3430","DOI":"10.1016\/j.cub.2017.09.066","article-title":"Glutamylation regulates transport, specializes function, and sculpts the structure of cilia.","volume":"27","author":"O\u2019Hagan","year":"2017","journal-title":"Curr. Biol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"684","DOI":"10.1016\/j.bone.2006.04.010","article-title":"Coordination of microtubules and the actin cytoskeleton is important in osteoclast function, but calcitonin disrupts sealing zones without affecting microtubule networks.","volume":"39","author":"Okumura","year":"2006","journal-title":"Bone"},{"key":"B28","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1083\/jcb.201603050","article-title":"The structured core of human \u03b2 tubulin confers isotype-specific polymerization properties.","volume":"213","author":"Pamula","year":"2016","journal-title":"J. Cell Biol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1038\/ncb3481","article-title":"Tubulin acetylation protects long-lived microtubules against mechanical ageing.","volume":"19","author":"Portran","year":"2017","journal-title":"Nat. Cell Biol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1093\/jmcb\/mjy031","article-title":"SNAP23\u2013Kif5 complex controls mGlu1 receptor trafficking.","volume":"10","author":"Raynaud","year":"2018","journal-title":"J. Mol. Cell Biol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"971","DOI":"10.1083\/jcb.152.5.971","article-title":"Regulation of Cdc42 gtpase by proline-rich tyrosine kinase 2 interacting with Psgap, a novel pleckstrin homology and src homology 3 domain containing rhogap protein.","volume":"152","author":"Ren","year":"2001","journal-title":"J. Cell Biol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1038\/nmeth.3047","article-title":"Improved vectors and genome-wide libraries for CRISPR screening","volume":"11","author":"Sanjana","year":"2014","journal-title":"Nat. Methods."},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202000740RR","article-title":"LSP1-myosin1e bimolecular complex regulates focal adhesion dynamics and cell migration.","volume":"35","author":"Sch\u00e4ringer","year":"2021","journal-title":"FASEB J"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-020-00917-z","article-title":"ARHGAP10, which encodes Rho GTPase-activating protein 10, is a novel gene for schizophrenia risk.","volume":"10","author":"Sekiguchi","year":"2020","journal-title":"Transl. Psychiatry"},{"key":"B35","doi-asserted-by":"publisher","first-page":"2026","DOI":"10.1242\/jcs.202036","article-title":"Time-lapse reveals that osteoclasts can move across the bone surface while resorbing.","volume":"130","author":"S\u00f8e","year":"2017","journal-title":"J. Cell. Sci."},{"key":"B36","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/S0091-679X(10)95003-6","article-title":"Characterization of anti-beta-tubulin antibodies.","volume":"95","author":"Spano","year":"2010","journal-title":"Methods Cell Biol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"18347","DOI":"10.1074\/jbc.M113.504894","article-title":"The Cdc42 guanine nucleotide exchange factor FGD6 coordinates cell polarity and endosomal membrane recycling in osteoclasts.","volume":"289","author":"Steenblock","year":"2014","journal-title":"J. Biol. Chem."},{"key":"B38","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1016\/j.devcel.2018.08.014","article-title":"Human \u03b2-tubulin isotypes can regulate microtubule protofilament number and stability.","volume":"47","author":"Ti","year":"2018","journal-title":"Dev. Cell"},{"key":"B39","doi-asserted-by":"publisher","first-page":"3449","DOI":"10.1242\/jcs.184622","article-title":"Tensin 3 is a new partner of Dock5 that controls osteoclast podosome organization and activity.","volume":"129","author":"Touaitahuata","year":"2016","journal-title":"J. Cell Sci."},{"key":"B40","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1038\/nmeth.3901","article-title":"The perseus computational platform for comprehensive analysis of (prote)omics data.","volume":"13","author":"Tyanova","year":"2016","journal-title":"Nat. Methods"},{"key":"B41","doi-asserted-by":"publisher","first-page":"3564","DOI":"10.1091\/mbc.E17-02-0124","article-title":"Tubulin isoform composition tunes microtubule dynamics.","volume":"28","author":"Vemu","year":"2017","journal-title":"Mol. Biol. Cell"},{"key":"B42","doi-asserted-by":"publisher","first-page":"12907","DOI":"10.1074\/jbc.C116.731133","article-title":"Structure and dynamics of single-isoform recombinant neuronal human tubulin.","volume":"291","author":"Vemu","year":"2016","journal-title":"J. Biol. Chem."},{"key":"B43","doi-asserted-by":"publisher","first-page":"1099","DOI":"10.1002\/jbmr.282","article-title":"The Rac1 exchange factor Dock5 is essential for bone resorption by osteoclasts.","volume":"26","author":"Vives","year":"2011","journal-title":"J. Bone Miner. Res."},{"key":"B44","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1126\/science.aai8764","article-title":"Microtubules acquire resistance from mechanical breakage through intralumenal acetylation.","volume":"356","author":"Xu","year":"2017","journal-title":"Science"},{"key":"B45","doi-asserted-by":"publisher","first-page":"1701","DOI":"10.1002\/jbmr.2851","article-title":"The actin-binding protein cofilin and its interaction with cortactin are required for podosome patterning in osteoclasts and bone resorption in vivo and in vitro.","volume":"31","author":"Zalli","year":"2016","journal-title":"J. Bone Miner. Res."}],"container-title":["Frontiers in Cell and Developmental Biology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2021.778887\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,18]],"date-time":"2021-11-18T04:52:34Z","timestamp":1637211154000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2021.778887\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,18]]},"references-count":45,"alternative-id":["10.3389\/fcell.2021.778887"],"URL":"https:\/\/doi.org\/10.3389\/fcell.2021.778887","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2021.09.17.460637","asserted-by":"object"}]},"ISSN":["2296-634X"],"issn-type":[{"value":"2296-634X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,18]]},"article-number":"778887"}}