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Meeting Report MEETING REPORT Exploring the pole: an EMBO conference on centrosomes and spindle pole bodies Sue L. Jaspersen and Tim Stearns The centrosome and spindle pole body community gathered for its triennial meeting from 12–16 September, 2008 at EMBL in Heidelberg (Germany). Sponsored by the EMBO, the conference on Centrioles are short, cylindrical structures in constituent proteins, and the identification centrosomes and spindle pole bodies was which the walls of the cylinder are made up of of those that are key functional components, organized by Trisha Davis, Susan Dutcher, nine specialized triplet microtubules. This elegant as opposed to hangers-on that use the centro- Michael Knop, Robert Palazzo, Elmar Schiebel nine-fold symmetry is absolutely conserved and some as a cellular assembly point. At the first and Kip Sluder. This was the fourth meeting gives centrioles their characteristic ‘pinwheel’ meeting twelve years ago, John Kilmartin’s in a series that started in 1996 and, as with the appearance in cross-section. Separate from their mass-spectrometry analysis of the SPB4 was previous meetings1–3, was an occasion to cel- role as a focus of PCM, centrioles also nucleate the a prescient first glimpse of the cornucopia of ebrate present accomplishments and contem- ciliary axoneme, imparting their nine-fold sym- centrosome proteins that would soon emerge plate the future. Below we summarize some of metry to this structure as well. A centriole at the from similar work on centrosomes, centrioles the major themes that emerged. base of a cilium is referred to as a basal body. and cilia. Whereas we once had the sense of The centrosome, with its pair of centrioles, having hold of only the trunk, leg or tail of the Centrosome 101 duplicates once per cell cycle at the G1/S tran- proverbial centrosomal elephant, new results Microtubules and their constellation of asso- sition so that a cell will have exactly two cen- are revealing a much more complete picture of ciated proteins and structures are strongly trosomes during mitosis. Centrioles reproduce the organelle as a whole. conserved components of all eukaryotic cells. semi-conservatively; the pairs separate and each Jens Andersen described a refinement of the One of the universal themes in the microtubule ‘mother’ centriole grows a new ‘daughter’ cen- original mass-spectrometry analysis of mamma- cytoskeleton is the use of specific structures to triole from its side. The centrosome has a mutu- lian centrosomes5, using SILAC stable isotope organize microtubules into useful arrays. The alistic relationship with the mitotic spindle, labelling technology to increase coverage and centrosome of animal cells and the spindle pole helping to form the poles of the spindle, while specificity of results from impure centrosome body of fungi are the two best characterized at the same time using that spindle to segregate material. Jean Cohen presented a compilation microtubule-organizing structures and were equally to the sister cells of a division. This equal of centriole and cilia proteomic data from across the topic of this meeting. The centrosome segregation of one centrosome per cell ensures the eukaryotic world and an associated web- contains a pair of centrioles surrounded by that each cell has the potential to grow a cilium, based analysis tool. In these and other proteomic a matrix of proteins involved in microtubule which is imparted by the mother centriole. studies, the same proteins come up repeatedly, nucleation and other centrosome functions. Most fungi have lost the capacity to make suggesting that, by analogy to genetic screens, This matrix of proteins is usually referred to as centrioles and cilia but have evolved a morpho- we are close to saturation for identification of pericentriolar material (PCM), although many logically distinct structure, known as the spindle new components. However, lest one become of the components of PCM are also found at pole body (SPB), to serve as their primary site of sanguine about this prospect, Hannah Müller’s other sites of microtubule organization in dif- microtubule nucleation. The functional orthol- proteomic analysis of centrosomes, isolated from ferentiated cell types. ogy of the SPB to the centrosome is reflected rapidly dividing Drosophila embryos, found only in the conservation of some of the important limited overlap with the list of known centro- Sue L. Jaspersen is at the Stowers Institute for Medical Research, Kansas City, MO 64110 USA components, and genetic and biochemical anal- some proteins from other systems. Perhaps and in the Department of Molecular and Integrative ysis of SPBs have provided valuable insight into this reflects differences in analysis techniques Physiology, University of Kansas Medical Center, centrosome regulation and function. or important biological changes in centrosome Kansas City, KS 66160 USA. Tim Stearns is in the Department of Biology, Stanford University, Stanford, components in the rapidly dividing embryo. CA 94305 USA and in the Department of Genetics, Centrosome parts Genetic analysis has also made an important Stanford University School of Medicine, Stanford, CA 94305 USA. e-mail: [email protected] and The rate-limiting step in understanding the contribution to identifying centrosome com- [email protected] centrosome has been the definition of its ponents and their interactions. The keynote NATURE CELL BIOLOGY VOLUME 10 | NUMBER 12 | DECEMBER 2008 1375 © 2008 Macmillan Publishers Limited. All rights reserved. MEETING REPORT SZY-20 SPD-2 Mps1 ZYG-1/Plk4 APC SCF Cdk2-cyclinA/E SAS-6 SAS-6-P SAS-4/CPAP SAS-5 Bld10/Cep135 G1/S cartwheel formation centriole assembly S M centriole Separase centriole elongation Plk1 disengagement, cytokinesis G2 and M centriole maturation & separation Bora Aurora-A Plk1 Recruitment of PCM, appendage, γ-TuRC, hPoc5, spindle pole proteins Figure 1 Centriole duplication pathway. Schematic representation of the major steps in centrosome duplication, as well as structural and regulatory proteins. We have combined results from several systems, and the details may differ in specific systems (for reviews of the centriole cycle and its cell-cycle control, see refs 18, 29–31). At the end of mitosis, each of the two engaged centrioles within each pair become disengaged by the action of the separase protease and Plk1. The older of the centrioles in each pair is marked with distal and sub-distal appendages, and the two centrioles remain linked by cohesion fibres. Centriole duplication is initiated at the disengaged centrioles during G1/S by SPD-2, as well as the kinases Mps1 and Cdk2–cyclinA/E. A key regulatory step in centriole duplication is activation of the kinase ZYG–1/Plk4; this involves control of its kinase activity, localization to the centrosome and, ultimately, proteolysis by the SCF ubiquitylation complex. Active ZYG–1/Plk4 can phosphorylate SAS-6, a component of the cartwheel structure at the base of nascent centrioles. Recruitment of SAS-6, SAS-5 and Bld10/Cep135 drive formation of the cartwheel, which imparts a nine-fold symmetry on the forming centriole. During S phase, centriole duplication continues by recruitment of SAS-4/CPAP. Levels of CPAP are tightly controlled during the cell cycle by APC-mediated proteolysis, perhaps restricting centriole assembly. Daughter centrioles continue to elongate during G2 and early M phase after activation of Aurora A at the centrosome, which is regulated by Plk1 and Bora. The centrin-binding protein hPoc5 is also recruited to the centrosome. The new mother centriole matures by addition of components of distal and subdistal appendages. The cohesion link between the two mother centrioles is broken, allowing the centrosomes to move to opposite sides of the nucleus. As mitosis begins, γ-tubulin ring complex (γ-TuRC) and other PCM components are recruited to the centrosomes, along with mitotic spindle pole proteins. The two mitotic centrosomes nucleate microtubules and help to form the mitotic spindle on which both chromosomes and centrosomes will segregate to the two daughter cells. At the end of mitosis, separase and Plk1 trigger centriole disengagement, allowing the centrioles to duplicate in the G1/S phase, and completing the cycle. address from Tony Hyman stressed the power Similar RNAi screens have been performed Interestingly, hPoc5 contains Sfi1-like repeats, of RNA interference (RNAi) in Caenorhabditis in Drosophila melanogaster cultured cells8,9. which were originally discovered as Cdc31/cen- elegans and mammalian cells as a tool for iden- Naomi Stevens described three genes, ana1, trin-binding motifs in the Saccharomyces cerevi- tifying important components and determining ana2 and ana3, that are involved in centrosome siae SPB component Sfi1. Recruitment of hPoc5 their function. Combining the ability to observe duplication and whose duplication results in to the distal lumen of centrioles, where centrin early embryonic divisions of C. elegans with anastral spindles. Ana2 is structurally similar 2/3 are located, occurs late in G2 and involves whole-genome RNAi, Hyman and his worm- to SAS-5, and like SAS-5 is required for centri- binding to its interacting partner, hPoc19, which ophile colleagues have discovered several of ole formation. Chad Pearson used basal body is recruited earlier in the cell cycle. the key players, including SAS-4 and SAS-6. He proteome data from Tetrahymena10 to identify described recent work revealing an unexpected Poc1 as a conserved centriole component that Centrosome pathways connection between centrosome size and spindle is also required for centrosome duplication One of the deeper mysteries of centrosome length, which was independent of microtubule and ciliogenesis in human cells. Using human biology is how the initiation of new centrioles nucleation. In addition, his group combined a centrin as the bait in a yeast two-hybrid screen, is controlled. As each centriole is potentially a mammalian RNAi screen6 with tagging of pro- Michel Bornens identified hPoc5, the human distinct centrosome, controlling initiation is teins in BACs7 to identify interaction networks orthologue of a protein originally identified in the key event in centrosome number control.
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