TY - JOUR T1 - Dynamic Kinetochore Size Regulation Promotes Microtubule Capture and Chromosome Biorientation in Mitosis JF - bioRxiv DO - 10.1101/279398 SP - 279398 AU - Carlos Sacristan AU - Misbha Ahmad AU - Jenny Keller AU - Job Fermie AU - Vincent Groenewold AU - Eelco Tromer AU - Alexander Fish AU - Roberto Melero AU - José María Carazo AU - Judith Klumperman AU - Andrea Musacchio AU - Anastassis Perrakis AU - Geert JPL Kops Y1 - 2018/01/01 UR - http://biorxiv.org/content/early/2018/03/12/279398.abstract N2 - Faithful chromosome segregation depends on the ability of sister kinetochores to attach to spindle microtubules. An outer layer of the kinetochore known as the fibrous corona transiently expands in early mitosis and disassembles upon microtubule capture. Neither the functional importance nor the mechanistic basis for this are known. Here we show that the dynein adaptor Spindly and the RZZ kinetochore complex drive fibrous corona formation in a dynein-independent manner. C-terminal farnesylation and MPS1 kinase activity cause conformational changes of Spindly that promote oligomerization of RZZ:Spindly complexes into a corona-like meshwork in cells and in vitro. Concurrent with corona expansion, Spindly potentiates corona shedding by recruiting dynein via three conserved short linear motifs. Expanded, non-sheddable fibrous coronas engage in extensive, long-lived lateral microtubule interactions that persist to metaphase and result in fused sister kinetochores, formation of merotelic attachments and chromosome segregation errors in anaphase. Thus, dynamic kinetochore size regulation in mitosis is coordinated by a single, Spindly-based mechanism that promotes initial microtubule capture and subsequent correct maturation of attachments. ER -