JCB_201708036 3003..3006

3003 The Rockefeller University Press J. Cell Biol. Vol. 216 No. 10 3003–3005 https://doi.org/10.1083/jcb.201708036 Meiosis is the process of specialized divisions that produce haploid gametes from diploid cells. Meiotic chromosome distribution is a critical event in sexual reproduction. Failure of chromosome segregation during meiosis results in progeny that are aneuploid, possessing chromosomes above or below the 2N number of the diploid genome. Such failures have many important consequences, not least of which is the high rate of aneuploid oocyte production in mammals, a central cause of human infertility, miscarriages, and birth defects (Bennabi et al., 2016). Beaven et al. examined the role of Drosophila melanogaster 14-3-3 proteins in meiotic chromosome segregation and found that they promote accurate assembly of meiotic spindles through spatial regulation of claret nondisjunctional (Ncd), a minus end–directed kinesin-14 family motor protein that mediates sliding of antiparallel microtubules and crosslinks parallel microtubules (Fink et al., 2009). This inhibition is relieved locally through phosphorylation by Aurora B, the kinase subunit of the chromosomal passenger complex (CPC)—a key regulator of spatial organization within meiotic and mitotic spindles (Weaver and Walczak, 2015; Radford et al., 2017b). Collectively, these findings reveal an intricate mechanism for organizing microtubules with the meiotic spindle to achieve accurate chromosome segregation. Female meiosis presents at least two sets of important challenges for accurate chromosome segregation (Bennabi et al., 2016). First, oocytes arrest in late prophase for extended periods of time, which can last for weeks to months in mice and up to several decades in humans. This arrest requires prolonged stability of both meiotic spindle structures and cell cycle regulatory states. Second, female meiotic spindles in many species, including humans, mice, frogs, and flies, lack centrosomes to direct their microtubule assembly and instead rely on cues from the chromosomes to guide spindle organization. Moreover, oocytes are larger than most somatic cells, and they divide asymmetrically, partitioning resources preferentially into the fertilized egg; this asymmetry necessitates precise formation of meiotic spindles adjacent and perpendicular to the cell cortex. Two pathways have been implicated as major contributors to chromatin-based signaling during acentrosomal spindle formation: the Ran pathway and CPC-mediated phosphorylation (Weaver and Walczak, 2015; Radford et al., 2017b). Although acentrosomal spindle assembly in different situations generally relies on one or both of these pathways, their relative importance can vary greatly between different organisms and situations (Radford et al., 2017b). Ran is a small GTPase whose nucleotide-binding state is controlled by a chromatin-bound exchange factor (RCC1) and a GTPase-activating protein (RanGAP1) that is cytoplasmic during interphase and dispersed or spindle associated during cell division. The distribution of these regulators results in higher levels of Ran-GTP within interphase nuclei and near chromosomes of dividing cells as well as lower levels in interphase cytoplasm and distal to condensed chromosomes during cell division. Ran controls the association of nuclear transport substrates to a family of nuclear transport receptors (called karyopherins) that also bind Ran-GTP. During interphase, this pathway drives a large fraction of nuclear– cytoplasmic protein trafficking. After nuclear envelope breakdown, the same interactions regulate numerous spindle assembly factors through karyopherin binding in a manner that is responsive to Ran-GTP levels and thus dictated by proximity to RCC1 localized on chromosomes. The CPC consists of four subunits: inner centromere protein (INC ENP), Survivin, Borealin/Dasra, and Aurora B kinase. The CPC complex concentrates on centromeres during early mitosis (Weaver and Walczak, 2015). The CPC is pivotal for the fidelity of chromosome segregation because it controls kinetochore structure, kinetochore–microtubule attachments, and signal transduction pathways that specify the timing of anaphase onset. The CPC localizes within a ring encircling the chromosomes during the first meiotic division (meiosis I), where it is essential for microtubule polymerization and spindle organization (Radford et al., 2012). During meiosis I, the CPC is also essential for centromere biorientation, i.e., the correct attachment of homologous chromosomes to microtubules emanating from opposite poles; notably, Drosophila meiotic biorientation is similarly dependent on Ncd function (Radford et al., 2012). Ncd modulates spindle length and morphology as well as pole organization in acentrosomal spindles (Radford et al., 2017b; She and Yang, 2017). Like other kinesin-14 proteins, During Drosophila melanogaster oogenesis, spindle assembly occurs without centrosomes and relies on signals from chromosomes. Beaven et al. (2017. J. Cell. Biol. https ://doi .org /10 .1083 /jcb .201704120) show that 14-3-3 proteins bind and inhibit a key microtubule motor, Ncd, during oogenesis, but Aurora B releases Ncd inhibition near chromosomes, allowing Ncd to work in the right time and place. Catch and release: 14-3-3 controls Ncd in meiotic spindles