{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T20:40:24Z","timestamp":1791232824619,"version":"4.1.0"},"reference-count":67,"publisher":"The Company of Biologists","license":[{"start":{"date-parts":[[2021,5,18]],"date-time":"2021-05-18T00:00:00Z","timestamp":1621296000000},"content-version":"am","delay-in-days":1964,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0"}],"funder":[{"DOI":"10.13039\/501100003391","name":"Fonds Unique Interminist\u00e9riel","doi-asserted-by":"publisher","award":["DiaTral"],"award-info":[{"award-number":["DiaTral"]}],"id":[{"id":"10.13039\/501100003391","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Conseil R?gional Languedoc-Roussillon","award":["Chercheur d'Avenir 2011"],"award-info":[{"award-number":["Chercheur d'Avenir 2011"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,1,1]]},"abstract":"<jats:p>In neurodegenerative diseases like Alzheimer's disease (AD), cell cycle defects and associated aneuploidy have been described. However, the importance of these defects in the physiopathology of AD and the underlying mechanistic processes are largely unknown in particular with respect to the microtubule-binding protein Tau, which is found in excess in the brain and cerebrospinal fluid of patients. Although it has long been known that Tau is phosphorylated during mitosis to generate a lower affinity for microtubules, there is, to our knowledge, no indication that an excess of this protein could affect mitosis. Here, we studied the effect of an excess of human Tau (hTau) protein on cell mitosis in vivo.<\/jats:p>\n               <jats:p>Using the Drosophila developing wing disc epithelium as a model, we show that an excess of hTau induces a mitotic arrest, with the presence of monopolar spindles. This mitotic defect leads to aneuploidy and apoptotic cell death. We studied the mechanism of action of hTau and found that the MT-binding domain of hTau is responsible for these defects. We also demonstrate that hTau effects occur via the inhibition of the function of the kinesin Klp61F, the Drosophila homologue of kinesin-5 (also called Eg5 or KIF11). We finally show that this deleterious effect of hTau is also found in other Drosophila cell types (neuroblasts) and tissues (the developing eye disc) as well as in human Hela cells.<\/jats:p>\n               <jats:p>By demonstrating that microtubule-bound Tau inhibits the Eg5\/KIF11 kinesin and cell mitosis, our work provides a new framework to consider the role of Tau in neurodegenerative diseases.<\/jats:p>","DOI":"10.1242\/dmm.022558","type":"journal-article","created":{"date-parts":[[2016,1,29]],"date-time":"2016-01-29T03:43:38Z","timestamp":1454039018000},"source":"Crossref","is-referenced-by-count":32,"title":["Tau excess impairs mitosis and kinesin-5 function, leading to aneuploidy and cell death"],"prefix":"10.1242","author":[{"given":"Anne-Laure","family":"Boug\u00e9","sequence":"first","affiliation":[{"name":"Institut de G\u00e9nomique Fonctionnelle, CNRS-UMR5203, INSERM-U1191, Universit\u00e9 Montpellier, 141 Rue de la Cardonille, Montpellier, Cedex 5, F-34094, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Laure","family":"Parmentier","sequence":"additional","affiliation":[{"name":"Institut de G\u00e9nomique Fonctionnelle, CNRS-UMR5203, INSERM-U1191, Universit\u00e9 Montpellier, 141 Rue de la Cardonille, Montpellier, Cedex 5, F-34094, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2021042513101659700_DMM022558C1","doi-asserted-by":"publisher","first-page":"4947","DOI":"10.1093\/hmg\/ddr432","article-title":"Functional genomic screen and network analysis reveal novel modifiers of tauopathy dissociated from tau phosphorylation","volume":"20","author":"Ambegaokar","year":"2011","journal-title":"Hum. 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