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| Open AccessThe evolution of centriole degradation in mouse sperm
Centrioles have a conserved structure and function but have diversified in sperm. Here the authors provide insight into the molecular mechanisms and adaptive evolution underlying this diversification.
- Sushil Khanal
- , Ankit Jaiswal
- & Tomer Avidor-Reiss
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Article
| Open AccessBICD2 phosphorylation regulates dynein function and centrosome separation in G2 and M
The dynein motor complex has a variety of important functions in both dividing and non-dividing cells. Here, Gallisà et al. describe a mode of regulation of dynein based on the phosphorylation of its adaptor BICD2 by the kinase PLK1, and how this is central for the regulation of centrosome position in G2 and M.
- Núria Gallisà-Suñé
- , Paula Sànchez-Fernàndez-de-Landa
- & Joan Roig
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Article
| Open AccessAn actin filament branching surveillance system regulates cell cycle progression, cytokinesis and primary ciliogenesis
The authors find that the ciliopathy-associated protein Oral-Facial-Digital syndrome 1 functions as a class II nucleation promoting factor to drive actin filament branching, required for cell cycle progression. Interferring with this function suppresses cancer cell growth.
- Muqing Cao
- , Xiaoxiao Zou
- & Qing Zhong
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Article
| Open AccessMicrotubule nucleation and γTuRC centrosome localization in interphase cells require ch-TOG
The molecular mechanisms underpinning the organization of microtubule arrays remain unclear. Here the authors show that in human cells, the microtubule polymerase ch-TOG promotes nucleation of microtubules at the interphase centrosome and the Golgi through a mechanism that involves transient interaction with the microtubule nucleator γTuRC.
- Aamir Ali
- , Chithran Vineethakumari
- & Jens Lüders
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Article
| Open AccessCEP128 is involved in spermatogenesis in humans and mice
CEP128 is a centrosomal protein important for the organization of centriolar microtubules. Here, the authors show that a CEP128 variant observed in human male siblings causes reduced sperm counts and morphologically abnormal sperm when modeled in mice, suggesting a role for CEP128 in male fertility.
- Xueguang Zhang
- , Lingbo Wang
- & Ying Shen
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Article
| Open AccessSub-centrosomal mapping identifies augmin-γTuRC as part of a centriole-stabilizing scaffold
The γ-tubulin ring complex (γTuRC) nucleates microtubules at the centrosome, but how this function is related to γTuRC subcentrosomal distribution is unclear. Here the authors show that γTuRC in the centriole lumen has a nucleation-independent role in centriole integrity and cilium assembly.
- Nina Schweizer
- , Laurence Haren
- & Jens Lüders
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Article
| Open AccessA dynamic basal complex modulates mammalian sperm movement
Centrioles are ancient organelles with a conserved architecture and their rigidity is thought to restrict microtubule sliding. Here authors show that, in mammalian sperm, the atypical distal centriole and its surrounding atypical pericentriolar matrix form a dynamic basal complex that facilitates a cascade of internal sliding deformations, coupling tail beating with asymmetric head kinking.
- Sushil Khanal
- , Miguel Ricardo Leung
- & Tomer Avidor-Reiss
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Article
| Open AccessHigh proliferation and delamination during skin epidermal stratification
How the developing skin epidermis is transformed from a simple single-layered epithelium to a complex and stratified barrier is still an open question. Here, the authors provide a model based on high proliferation and delamination of the keratinocyte progenitors that support the stratification process.
- Mareike Damen
- , Lisa Wirtz
- & Hisham Bazzi
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Article
| Open AccessFibrogranular materials function as organizers to ensure the fidelity of multiciliary assembly
Multicilia are complex, and how they achieve accurate assembly is unclear. Here, the authors show that fibrogranular materials condense into spherical cores and function in multicilia formation by tightly associating with deuterosomes and concentrating specific proteins to promote proper assembly.
- Huijie Zhao
- , Qingxia Chen
- & Xueliang Zhu
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Article
| Open AccessMild replication stress causes chromosome mis-segregation via premature centriole disengagement
Chromosome instability can be caused by replication stress, although the mechanism is unclear. Here, the authors show that inducing mild replication stress in cancerous and non-cancerous cell lines leads to centriole disengagement and the subsequent formation of lagging chromosomes and micronuclei.
- Therese Wilhelm
- , Anna-Maria Olziersky
- & Patrick Meraldi
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Article
| Open AccessAtypical function of a centrosomal module in WNT signalling drives contextual cancer cell motility
Centrosomes function in cell migration by organizing microtubules. Here, Luo et al. surprisingly show that centrosome proteins also control migration after recruitment by Wnt-PCP proteins to the cell cortex, leading to actin remodelling and protrusive activity relevant to aggressive cancer motility.
- Yi Luo
- , Miriam Barrios-Rodiles
- & Laurence Pelletier
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Article
| Open AccessActo-myosin force organization modulates centriole separation and PLK4 recruitment to ensure centriole fidelity
Centriolar separation is thought to be crucial for centriole duplication, but the mechanism behind separation is poorly understood. Here, using micropatterning, the authors report that actomyosin forces influence the direction, distance, and time of centriole separation.
- Elisa Vitiello
- , Philippe Moreau
- & Martial Balland
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Article
| Open AccessM-Phase Phosphoprotein 9 regulates ciliogenesis by modulating CP110-CEP97 complex localization at the mother centriole
Ciliogenesis is negatively regulated by the CP110-CEP97 complex, although the mechanism controlling mother centriole localization is poorly understood. Here, Huang et al. show that KIF24 recruits MMP9 to the mother centriole, where it regulates ciliogenesis by controlling CP110-CEP97 recruitment.
- Ning Huang
- , Donghui Zhang
- & Jianguo Chen
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Article
| Open AccessRecruitment of the mitotic exit network to yeast centrosomes couples septin displacement to actomyosin constriction
The Mitotic Exit Network (MEN) promotes mitotic exit and cytokinesis but if and how MEN independently controls these two processes is unclear. Here, the authors report that MEN displaces septins from the cell division site to promote actomyosin ring constriction, independently of MEN control of mitotic exit.
- Davide Tamborrini
- , Maria Angeles Juanes
- & Simonetta Piatti
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Article
| Open AccessEpendymal cilia beating induces an actin network to protect centrioles against shear stress
Ependymal ciliary beating contributes to the flow of cerebrospinal fluid in the brain ventricles and these cilia resist the flow forces. Here the authors show that the assembly of a dense actin network around the centrioles is induced by cilia beating to protect centrioles against the shear stress generated by ciliary motility.
- Alexia Mahuzier
- , Asm Shihavuddin
- & Nathalie Delgehyr
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Article
| Open AccessA novel atypical sperm centriole is functional during human fertilization
The two zygote centrioles are paternally inherited; however, their development is incompletely understood. Here, the authors show that the distal centriole is remodeled into an atypical centriole which functions as the zygote’s second centriole.
- Emily L. Fishman
- , Kyoung Jo
- & Tomer Avidor-Reiss
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| Open AccessSuper-resolution architecture of mammalian centriole distal appendages reveals distinct blade and matrix functional components
Distal appendages (DAPs) at the cilia base mediate membrane docking during ciliogenesis. Here the authors use super-resolution microscopy to map 16 centriole distal end components, revealing the structure of the backbone of the DAP, as well as a previously undescribed distal appendage matrix.
- T. Tony Yang
- , Weng Man Chong
- & Jung-Chi Liao
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Article
| Open AccessDirect binding of CEP85 to STIL ensures robust PLK4 activation and efficient centriole assembly
Centriole duplication is tightly regulated in vivo, but the underlying molecular mechanisms are incompletely understood. Here the authors use high-resolution structural and imaging methods to show that CEP85 directly interacts with STIL and mediates efficient centriolar targeting of STIL, PLK4 activation and centriole assembly.
- Yi Liu
- , Gagan D. Gupta
- & Mark van Breugel
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| Open AccessOver-elongation of centrioles in cancer promotes centriole amplification and chromosome missegregation
Cancer cells are characterised by abnormalities in the number of centrosomes and this phenotype is linked with tumorigenesis. Here the authors report centriole length deregulation in a subset of cancer cell lines and suggest a link with subsequent alterations in centriole numbers and chromosomal instability.
- Gaëlle Marteil
- , Adan Guerrero
- & Mónica Bettencourt-Dias
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| Open AccessHuman microcephaly protein RTTN interacts with STIL and is required to build full-length centrioles
Mutations in many centriolar protein-encoding genes cause primary microcephaly. Here the authors show that human microcephaly protein RTTN directly interacts with STIL and acts downstream of STIL-mediated centriole assembly, contributing to building full-length centrioles
- Hsin-Yi Chen
- , Chien-Ting Wu
- & Tang K. Tang
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Article
| Open AccessPrecocious centriole disengagement and centrosome fragmentation induced by mitotic delay
The spindle assembly checkpoint delays mitotic progression until sister chromatids are bi-oriented. Here the authors show that moderate delays in mitotic progression induce centrosome fragmentation and centriole disengagement and that spindle bipolarity is ensured by HSET-mediated spindle pole clustering.
- Menuka Karki
- , Neda Keyhaninejad
- & Charles B. Shuster
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Article
| Open AccessStat3 regulates centrosome clustering in cancer cells via Stathmin/PLK1
Cancer cells have amplified centrosomes and deal with this abnormality by clustering them together so that they can be segregated in daughter cells. Here the authors perform a screening looking for inhibitors of this clustering process and find that STAT3 regulates this process independently of its transcriptional function.
- Edward J. Morris
- , Eiko Kawamura
- & Shoukat Dedhar
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Article
| Open AccessHierarchical assembly of centriole subdistal appendages via centrosome binding proteins CCDC120 and CCDC68
Centriole subdistal appendages (SDAs) anchor microtubules in interphase cells, but their composition and assembly mechanisms are unclear. Here the authors show that two new SDA components, CCDC120 and CCDC68, are required for hierarchical SDA assembly and centrosome microtubule anchoring.
- Ning Huang
- , Yuqing Xia
- & Jianguo Chen
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| Open AccessCell-free reconstitution reveals centriole cartwheel assembly mechanisms
The centriole is an organelle composed of rings of SAS-6 proteins that form a cartwheel structure. Here the authors develop a cell-free system to examine core cartwheel assembly ofC. reinhardtiiproteins and discover that CrSAS-6 has autonomous properties that facilitates self-organized stacking of pairs of rings.
- P. Guichard
- , V. Hamel
- & P. Gönczy
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| Open AccessExpression of the novel maternal centrosome assembly factor Wdr8 is required for vertebrate embryonic mitoses
The assembly of the first centrosome occurs upon fertilisation when male centrioles recruit pericentriolar material from the egg cytoplasm. Here the authors identify Wdr8 as a maternally essential protein that is required for centrosome assembly during embryonic mitoses of medaka.
- Daigo Inoue
- , Manuel Stemmer
- & Oliver J. Gruss
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Article
| Open AccessAutophagy controls centrosome number by degrading Cep63
The ubiquitin-proteasome system is thought to be the primary regulator of centrosome number. Here, Watanabe et al. show that selective autophagy also plays a role in regulating centrosome number via p62-dependent recruitment of centrosomal protein 63 to autophagosomes.
- Yuichiro Watanabe
- , Shinya Honda
- & Shigeomi Shimizu
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Article
| Open AccessA centrosome interactome provides insight into organelle assembly and reveals a non-duplication role for Plk4
The centrosome is a large intracellular structure that serves as the microtubule-organising center, but how it is accurately assembled is not known. Here the authors generate a ‘domain-level’ centrosome interactome and show that Plk4 positions the essential centriole component Asterless by phosphorylating Cep135.
- Brian J. Galletta
- , Carey J. Fagerstrom
- & Nasser M. Rusan
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| Open AccessAurora-A recruitment and centrosomal maturation are regulated by a Golgi-activated pool of Src during G2
The Golgi mitotic checkpoint couples Golgi inheritance with cell cycle transition, and regulates centrosomal recruitment of the mitotic kinase Aurora-A. Here the authors show that upon Golgi ribbon fragmentation in G2, Src phosphorylates Aurora-A at the Golgi, driving its localization to the centrosomes.
- Maria Luisa Barretta
- , Daniela Spano
- & Antonino Colanzi
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Article
| Open AccessActin nucleation at the centrosome controls lymphocyte polarity
Cell polarity is marked by re-orientation of the centrosome, but the mechanisms governing centrosome polarization are poorly understood. Here Obino et al. show that in lymphocytes centrosome-associated Arp2/3 nucleates actin that tethers the centrosome to the nucleus; activation depletes Arp2/3 from the centrosome and frees it from the nucleus.
- Dorian Obino
- , Francesca Farina
- & Ana-Maria Lennon-Duménil
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| Open AccessA CEP215–HSET complex links centrosomes with spindle poles and drives centrosome clustering in cancer
Centrosome clustering allows survival of cells with amplified centrosomes at the cost of chromosome instability. Here, Chavali et al. show that the centrosome component CEP215 collaborates with the kinesin motor HSET both to maintain spindle poles connections and to cluster centrosomes.
- Pavithra L. Chavali
- , Gayathri Chandrasekaran
- & Fanni Gergely
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Article
| Open AccessLoss of KLF14 triggers centrosome amplification and tumorigenesis
Centrosome amplification is common in cancer, but the mechanism is not clear. Here the authors uncover a role for Kruppel-like factor 14 (KLF14) as a transcriptional repressor of polo-like kinase 4 (PLK4); KLF14 depletion correlates with increased PLK4 in human samples and leads to centrosome amplification and tumorigenesis in mice.
- Guangjian Fan
- , Lianhui Sun
- & Chuangui Wang
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| Open AccessPlk1 relieves centriole block to reduplication by promoting daughter centriole maturation
The orthogonal orientation between centrioles is thought to prevent their reduplication. Shukla et al.show that Polo-like kinase 1-dependent daughter centriole maturation, reflected in increasing inter-centriolar distance, allows centriole reduplication prior to loss of orthogonal orientation.
- Anil Shukla
- , Dong Kong
- & Jadranka Loncarek
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CEP63 deficiency promotes p53-dependent microcephaly and reveals a role for the centrosome in meiotic recombination
CEP63 is a centrosomal protein that is mutated in the microcephaly disease Seckel syndrome. Here the authors disrupt Cep63 in the mouse and find that neural progenitor cells undergo p53-dependent cell death, and uncover a role for CEP63 in ensuring correct meiotic recombination in male gametes.
- Marko Marjanović
- , Carlos Sánchez-Huertas
- & Travis H. Stracker
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| Open AccessA three-step MTOC fragmentation mechanism facilitates bipolar spindle assembly in mouse oocytes
Mitotic spindles assemble from two centrosomes, but oocytes lack centrosomes so how their spindles assemble is unclear. Here Clift and Schuh show that multiple acentriolar microtubule-organizing centres fragment in a three-step process to facilitate bipolar spindle assembly in mouse oocytes.
- Dean Clift
- & Melina Schuh
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| Open AccessCdk1 phosphorylates the Rac activator Tiam1 to activate centrosomal Pak and promote mitotic spindle formation
Centrosome separation, promoted by the kinesin Eg5, is antagonized by the guanine nucleotide exchange factor Tiam1 through an unknown mechanism. Here Whalley et al. show that Tiam1 is phosphorylated by cyclin-dependent kinase 1 in prophase, leading to downstream activation of p21-activated kinases (PAKs).
- Helen J. Whalley
- , Andrew P. Porter
- & Angeliki Malliri
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The deubiquitinating enzyme CYLD controls apical docking of basal bodies in ciliated epithelial cells
Mutations in the deubiquitinase gene CYLD are associated with cylindromatosis, a disease characterized by the development of skin appendage tumours. Eguether et al.discover that CYLD localizes to centrosomes and is required for basal body migration and docking, providing insight into its tumour suppressor activity.
- Thibaut Eguether
- , Maria A. Ermolaeva
- & Anne-Marie Tassin
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APC/C is an essential regulator of centrosome clustering
Cells with multiple centrosomes, as are often observed in cancer, can still divide successfully because the centrosomes cluster to form a single spindle pole body. Drosopoulos et al.show that degradation of the kinesin Eg5 by APC/C-CDH1 is required for centrosome clustering.
- Konstantinos Drosopoulos
- , Chan Tang
- & Spiros Linardopoulos
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SAPK pathways and p53 cooperatively regulate PLK4 activity and centrosome integrity under stress
Centrosome duplication during cell division is controlled by the polo-like kinase PLK4. Nakamura et al. reveal how stress-activated protein kinase and the tumour suppressor p53 act together to regulate PLK4, and show that their combined loss in cancer cells leads to the appearance of supernumerary centrosomes.
- Takanori Nakamura
- , Haruo Saito
- & Mutsuhiro Takekawa
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LGALS3BP regulates centriole biogenesis and centrosome hypertrophy in cancer cells
Dysregulation of centrosome size and number is frequently associated with cancer. Fogeron et al. construct a protein-interaction network to identify proteins that are relevant for centrosome abnormalities in cancer, and show that deregulation of LGALS3BP affects centrosomal biogenesis.
- Marie-Laure Fogeron
- , Hannah Müller
- & Bodo M.H. Lange
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Sas-4 provides a scaffold for cytoplasmic complexes and tethers them in a centrosome
Cell division and cilium formation are dependent on centrosomes that consist of two centrioles and pericentriolar material (PCM). In this study, the Sas-4 protein is shown to be important in mediating the formation of cytoplasmic PCM complexes and the incorporation of this material into centrosomes.
- Jayachandran Gopalakrishnan
- , Vito Mennella
- & Tomer Avidor-Reiss
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Article
| Open AccessDrosophila neuroblasts retain the daughter centrosome
Asymmetric partitioning of centrosomes has been reported inDrosophilaneuroblasts, but whether this type of division has implications for stem cell self-renewal is unclear. In this study, the authors show that the asymmetric division of the centrosomes correlates with the asymmetric fate of the cells and that the daughter centrosome is retained by the neuroblast.
- Jens Januschke
- , Salud Llamazares
- & Cayetano Gonzalez