{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T13:57:09Z","timestamp":1768485429495,"version":"3.49.0"},"posted":{"date-parts":[[2018,3,15]]},"group-title":"Cell Biology","reference-count":48,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2018,3,15]]},"abstract":"<jats:title>SUMMARY<\/jats:title>\n                <jats:p>\n                  The kinetochore is a dynamic multi-protein assembly that forms on each sister chromatid and interacts with microtubules of the mitotic spindle to drive chromosome segregation. In animals, kinetochores without attached microtubules expand their outermost layer into crescent and ring shapes to promote microtubule capture and spindle assembly checkpoint (SAC) signalling. Kinetochore expansion is an example of protein co-polymerization, but the mechanism is not understood. Here, we present evidence that kinetochore expansion is driven by oligomerization of the Rod-Zw10-Zwilch (RZZ) complex, an outer kinetochore component that recruits the motor dynein and the SAC proteins Mad1-Mad2. Depletion of ROD in human cells suppresses kinetochore expansion, as does depletion of Spindly, the adaptor that connects RZZ to dynein, while dynein itself is dispensable. Expansion is also suppressed by mutating ZWILCH residues implicated in Spindly binding. Conversely, supplying cells with excess ROD facilitates kinetochore expansion under otherwise prohibitive conditions. Using the\n                  <jats:italic>C. elegans<\/jats:italic>\n                  early embryo, we demonstrate that ROD-1 has a concentration-dependent propensity for oligomerizing into\n                  <jats:italic>\u00b5<\/jats:italic>\n                  m-scale filaments, and we identify the ROD-1 \u03b2-propeller as a key regulator of self-assembly. Finally, we show that a minimal ROD-1-Zw10 complex efficiently oligomerizes into filaments\n                  <jats:italic>in vitro<\/jats:italic>\n                  . Our results suggest that RZZ\u2019s capacity for oligomerization is harnessed by kinetochores to assemble the expanded outermost domain, in which RZZ filaments serve as recruitment platforms for SAC components and microtubule-binding proteins. Thus, we propose that RZZ self-assembly into filaments underlies the adaptive change in kinetochore size that contributes to chromosome segregation fidelity.\n                <\/jats:p>","DOI":"10.1101\/282707","type":"posted-content","created":{"date-parts":[[2018,3,15]],"date-time":"2018-03-15T06:30:30Z","timestamp":1521095430000},"source":"Crossref","is-referenced-by-count":2,"title":["Self-assembly of the RZZ complex into filaments drives kinetochore expansion in the absence of microtubule attachment"],"prefix":"10.64898","author":[{"given":"Cl\u00e1udia","family":"Pereira","sequence":"first","affiliation":[]},{"given":"Rita M.","family":"Reis","sequence":"additional","affiliation":[]},{"given":"Jos\u00e9 B.","family":"Gama","sequence":"additional","affiliation":[]},{"given":"Dhanya K.","family":"Cheerambathur","sequence":"additional","affiliation":[]},{"given":"Ana X.","family":"Carvalho","sequence":"additional","affiliation":[]},{"given":"Reto","family":"Gassmann","sequence":"additional","affiliation":[]}],"member":"54368","reference":[{"key":"2019072208554770000_282707v1.1","doi-asserted-by":"crossref","first-page":"13","DOI":"10.3390\/biology6010013","article-title":"Mechanisms of chromosome congression during mitosis","volume":"6","year":"2017","journal-title":"Biology"},{"key":"2019072208554770000_282707v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2015.08.051"},{"key":"2019072208554770000_282707v1.3","doi-asserted-by":"publisher","DOI":"10.3390\/biology6010005"},{"key":"2019072208554770000_282707v1.4","doi-asserted-by":"crossref","first-page":"597","DOI":"10.3934\/molsci.2016.4.597","article-title":"The mitotic checkpoint complex (MCC): looking back and forth after 15 years","volume":"3","year":"2016","journal-title":"AIMS Mol. Sci"},{"key":"2019072208554770000_282707v1.5","doi-asserted-by":"crossref","first-page":"e05269","DOI":"10.7554\/eLife.05269","article-title":"A molecular basis for the differential roles of Bub1 and BubR1 in the spindle assembly checkpoint","volume":"4","year":"2015","journal-title":"eLife"},{"key":"2019072208554770000_282707v1.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2005.01.038"},{"key":"2019072208554770000_282707v1.7","doi-asserted-by":"publisher","DOI":"10.1038\/nature21384"},{"key":"2019072208554770000_282707v1.8","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.22513"},{"key":"2019072208554770000_282707v1.9","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201311015"},{"key":"2019072208554770000_282707v1.10","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms15822"},{"key":"2019072208554770000_282707v1.11","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1687508"},{"key":"2019072208554770000_282707v1.12","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms8162"},{"key":"2019072208554770000_282707v1.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2017.10.011"},{"key":"2019072208554770000_282707v1.14","doi-asserted-by":"publisher","DOI":"10.1098\/rsob.150160"},{"key":"2019072208554770000_282707v1.15","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201610108"},{"key":"2019072208554770000_282707v1.16","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201611060"},{"key":"2019072208554770000_282707v1.17","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2015.11.012"},{"key":"2019072208554770000_282707v1.18","doi-asserted-by":"publisher","DOI":"10.1016\/S0074-7696(08)61672-1"},{"key":"2019072208554770000_282707v1.19","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1002\/(SICI)1097-0169(1996)35:2<121::AID-CM5>3.0.CO;2-D","article-title":"Modulation of CENP-E organization at kinetochores by spindle microtubule attachment","volume":"35","year":"1996","journal-title":"Cytoskeleton"},{"key":"2019072208554770000_282707v1.20","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.12.7.1995"},{"key":"2019072208554770000_282707v1.21","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201506020"},{"key":"2019072208554770000_282707v1.22","doi-asserted-by":"publisher","DOI":"10.1038\/ncb3223"},{"key":"2019072208554770000_282707v1.23","doi-asserted-by":"publisher","DOI":"10.1007\/s004120050266"},{"key":"2019072208554770000_282707v1.24","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-22164-5"},{"key":"2019072208554770000_282707v1.25","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.130.4.941"},{"key":"2019072208554770000_282707v1.26","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E04-06-0486"},{"key":"2019072208554770000_282707v1.27","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1331"},{"key":"2019072208554770000_282707v1.28","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2093"},{"key":"2019072208554770000_282707v1.29","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2010.02.014"},{"key":"2019072208554770000_282707v1.30","doi-asserted-by":"publisher","DOI":"10.1016\/j.sbi.2007.03.010"},{"key":"2019072208554770000_282707v1.31","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-biochem-061516-044643"},{"key":"2019072208554770000_282707v1.32","doi-asserted-by":"publisher","DOI":"10.1126\/science.1246232"},{"key":"2019072208554770000_282707v1.33","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200411118"},{"key":"2019072208554770000_282707v1.34","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E08-10-1047"},{"key":"2019072208554770000_282707v1.35","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.142.3.763"},{"key":"2019072208554770000_282707v1.36","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2005.05.003"},{"key":"2019072208554770000_282707v1.37","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2005.03.052"},{"key":"2019072208554770000_282707v1.38","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2017.03.025"},{"key":"2019072208554770000_282707v1.39","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200105093"},{"key":"2019072208554770000_282707v1.40","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1101-1001"},{"key":"2019072208554770000_282707v1.41","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2014.07.011"},{"key":"2019072208554770000_282707v1.42","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0016494"},{"key":"2019072208554770000_282707v1.43","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1886810"},{"key":"2019072208554770000_282707v1.44","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E09-04-0356"},{"key":"2019072208554770000_282707v1.45","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.113.156299"},{"key":"2019072208554770000_282707v1.46","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1038\/nmeth.2641","article-title":"Engineering the Caenorhabditis elegans genome using Cas9-triggered homologous recombination","volume":"10","year":"2013","journal-title":"Nat. Meth"},{"key":"2019072208554770000_282707v1.47","doi-asserted-by":"crossref","first-page":"e1006941","DOI":"10.1371\/journal.pgen.1006941","article-title":"Dynactin binding to tyrosinated microtubules promotes centrosome centration in C. elegans by enhancing dynein-mediated organelle transport","volume":"13","year":"2017","journal-title":"PLOS Genetics"},{"key":"2019072208554770000_282707v1.48","doi-asserted-by":"crossref","unstructured":"Bieniossek, C. , Richmond, T.J. , and Berger, I. (2008). MultiBac: multigene baculovirus-based eukaryotic protein complex production. Curr. Protoc. Protein Sci. Chapter 5, Unit 5.20.","DOI":"10.1002\/0471140864.ps0520s51"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/282707","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T23:23:50Z","timestamp":1768433030000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/282707"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,3,15]]},"references-count":48,"URL":"https:\/\/doi.org\/10.1101\/282707","relation":{"is-preprint-of":[{"id-type":"doi","id":"10.1016\/j.cub.2018.08.056","asserted-by":"subject"}]},"subject":[],"published":{"date-parts":[[2018,3,15]]},"subtype":"preprint"}}