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Seminars in Cell & Developmental Biology Sep 2021Centrosomes were first described by Edouard Van Beneden and named and linked to chromosome segregation by Theodor Boveri around 1870. In the 1960-1980s, electron... (Review)
Review
Centrosomes were first described by Edouard Van Beneden and named and linked to chromosome segregation by Theodor Boveri around 1870. In the 1960-1980s, electron microscopy studies have revealed the remarkable ultrastructure of a centriole -- a nine-fold symmetrical microtubular assembly that resides within a centrosome and organizes it. Less than two decades ago, proteomics and genomic screens conducted in multiple species identified hundreds of centriole and centrosome core proteins and revealed the evolutionarily conserved nature of the centriole assembly pathway. And now, super resolution microscopy approaches and improvements in cryo-tomography are bringing an unparalleled nanoscale-detailed picture of the centriole and centrosome architecture. In this chapter, we summarize the current knowledge about the architecture of human centrioles. We discuss the structured organization of centrosome components in interphase, focusing on localization/function relationship. We discuss the process of centrosome maturation and mitotic spindle pole assembly in centriolar and acentriolar cells, emphasizing recent literature.
Topics: Centrioles; Centrosome; Humans; Interphase
PubMed: 33836946
DOI: 10.1016/j.semcdb.2021.03.020 -
Current Biology : CB Oct 2018During the cell cycle it is critical that the duplicated DNA faithfully segregates to give rise to two genetically identical daughter cells. An even distribution of the... (Review)
Review
During the cell cycle it is critical that the duplicated DNA faithfully segregates to give rise to two genetically identical daughter cells. An even distribution of the genome during mitosis is mediated by mitotic spindle microtubules, assisted by, among others, motor proteins of the kinesin superfamily. Chromokinesins are members of the kinesin superfamily that harbour a specific DNA-binding domain. The best characterized chromokinesins belong to the kinesin-4/Kif4 and kinesin-10/Kif22 families, respectively. Functional analysis of chromokinesins in several model systems revealed their involvement in chromosome arm orientation and oscillations. This is consistent with their originally proposed role in the generation of polar ejection forces that assist chromosome congression to the spindle equator. Kinesin-12/Kif15 members comprise a third family of chromokinesins, but their role remains less understood. Noteworthy, all chromokinesins exhibit chromosome-independent localization on spindle microtubules, and recent works have significantly extended the portfolio of mitotic processes in which chromokinesins play a role, from error correction and DNA compaction, to the regulation of spindle microtubule dynamics.
Topics: Cell Division; Chromosome Segregation; Chromosomes; DNA-Binding Proteins; Dyneins; Humans; Kinesins; Kinetochores; Microtubules; Mitosis; Nuclear Proteins; Spindle Apparatus; Spindle Poles
PubMed: 30300593
DOI: 10.1016/j.cub.2018.07.017 -
Philosophical Transactions of the Royal... Sep 2014Centrosomes-as well as the related spindle pole bodies (SPBs) of yeast-have been extensively studied from the perspective of their microtubule-organizing roles.... (Review)
Review
Centrosomes-as well as the related spindle pole bodies (SPBs) of yeast-have been extensively studied from the perspective of their microtubule-organizing roles. Moreover, the biogenesis and duplication of these organelles have been the subject of much attention, and the importance of centrosomes and the centriole-ciliary apparatus for human disease is well recognized. Much less developed is our understanding of another facet of centrosomes and SPBs, namely their possible role as signalling centres. Yet, many signalling components, including kinases and phosphatases, have been associated with centrosomes and spindle poles, giving rise to the hypothesis that these organelles might serve as hubs for the integration and coordination of signalling pathways. In this review, we discuss a number of selected studies that bear on this notion. We cover different processes (cell cycle control, development, DNA damage response) and organisms (yeast, invertebrates and vertebrates), but have made no attempt to be comprehensive. This field is still young and although the concept of centrosomes and SPBs as signalling centres is attractive, it remains primarily a concept-in need of further scrutiny. We hope that this review will stimulate thought and experimentation.
Topics: Animals; Cell Cycle; Centrosome; Humans; Mitosis; Models, Biological; Signal Transduction; Species Specificity; Spindle Pole Bodies; Yeasts
PubMed: 25047618
DOI: 10.1098/rstb.2013.0464 -
Cells May 2022The process of chromosome congression and alignment is at the core of mitotic fidelity. In this review, we discuss distinct spatial routes that the chromosomes take to... (Review)
Review
The process of chromosome congression and alignment is at the core of mitotic fidelity. In this review, we discuss distinct spatial routes that the chromosomes take to align during prometaphase, which are characterized by distinct biomolecular requirements. Peripheral polar chromosomes are an intriguing case as their alignment depends on the activity of kinetochore motors, polar ejection forces, and a transition from lateral to end-on attachments to microtubules, all of which can result in the delayed alignment of these chromosomes. Due to their undesirable position close to and often behind the spindle pole, these chromosomes may be particularly prone to the formation of erroneous kinetochore-microtubule interactions, such as merotelic attachments. To prevent such errors, the cell employs intricate mechanisms to preposition the spindle poles with respect to chromosomes, ensure the formation of end-on attachments in restricted spindle regions, repair faulty attachments by error correction mechanisms, and delay segregation by the spindle assembly checkpoint. Despite this protective machinery, there are several ways in which polar chromosomes can fail in alignment, mis-segregate, and lead to aneuploidy. In agreement with this, polar chromosomes are present in certain tumors and may even be involved in the process of tumorigenesis.
Topics: Chromosome Segregation; Kinetochores; Microtubules; Mitosis; Spindle Apparatus
PubMed: 35563837
DOI: 10.3390/cells11091531 -
Cold Spring Harbor Perspectives in... Feb 2015The centrosome was discovered in the late 19th century when mitosis was first described. Long recognized as a key organelle of the spindle pole, its core component, the... (Review)
Review
The centrosome was discovered in the late 19th century when mitosis was first described. Long recognized as a key organelle of the spindle pole, its core component, the centriole, was realized more than 50 or so years later also to comprise the basal body of the cilium. Here, we chart the more recent acquisition of a molecular understanding of centrosome structure and function. The strategies for gaining such knowledge were quickly developed in the yeasts to decipher the structure and function of their distinctive spindle pole bodies. Only within the past decade have studies with model eukaryotes and cultured cells brought a similar degree of sophistication to our understanding of the centrosome duplication cycle and the multiple roles of this organelle and its component parts in cell division and signaling. Now as we begin to understand these functions in the context of development, the way is being opened up for studies of the roles of centrosomes in human disease.
Topics: Animals; Centrosome; Cilia; Drosophila; Drosophila Proteins; Humans; Mice; Mitosis; Models, Biological; Protein Serine-Threonine Kinases; S Phase; Saccharomycetales; Spindle Apparatus; Xenopus laevis
PubMed: 25646378
DOI: 10.1101/cshperspect.a015800 -
Cells Dec 2022The centrosome consists of two centrioles surrounded by pericentriolar material [...].
The centrosome consists of two centrioles surrounded by pericentriolar material [...].
Topics: Centrosome; Centrioles
PubMed: 36497189
DOI: 10.3390/cells11233931 -
Reproduction (Cambridge, England) Mar 2020Acentriolar microtubule-organizing centers (aMTOCs) play a critical role in stable meiotic spindle assembly in oocytes, necessary for accurate chromosome segregation....
Acentriolar microtubule-organizing centers (aMTOCs) play a critical role in stable meiotic spindle assembly in oocytes, necessary for accurate chromosome segregation. Yet, there is a limited understanding of the essential regulatory components of these unique MTOCs. In somatic cells, CEP215 (Centrosomal Protein 215) serves as an important regulator of centrosome maturation and spindle organization. Here, we assessed whether it has a similar function in mouse oocytes. CEP215 was detected in oocyte lysates and specifically localized to aMTOCs throughout the progression of meiosis in a pericentrin-dependent manner. Super-resolution microscopy revealed CEP215 co-localization with pericentrin and a unique pore/ring-like structural organization of aMTOCs. Interestingly, inhibition of Aurora Kinase A in either MI or MII-stage oocytes resulted in a striking loss of the ring-like aMTOC organization and pronounced CEP215 clustering at spindle poles, as well as shorter spindles with highly focused poles. In vitro siRNA-mediated transcript knockdown effectively reduced CEP215 in approximately 85% of the oocytes. Maturation rates to MII were similar in the Cep215 siRNA and injected controls; however, a high percentage (~40%) of the Cep215-knockdown oocytes showed notable variations in spindle pole focusing. Surprisingly, pericentrin and γ-tubulin localization and fluorescence intensity at aMTOCs were unaltered in knockdown oocytes, contrasting with mitotic cells where CEP215 depletion reduced γ-tubulin at centrosomes. Our results demonstrate that CEP215 is a functional component of oocyte aMTOCs and participates in the regulation of meiotic spindle pole focusing. Moreover, these studies reveal a vital role for Aurora Kinase A activity in the maintenance of aMTOC organization in oocytes.
Topics: Animals; Antigens; Aurora Kinase A; Cell Cycle Proteins; Female; Male; Meiosis; Mice, Inbred C57BL; Microtubule-Organizing Center; Oocytes; Tubulin
PubMed: 31895686
DOI: 10.1530/REP-19-0263 -
Current Biology : CB Oct 2013
Topics: Microtubules; Mitosis; Nuclear Envelope; Saccharomyces cerevisiae; Schizosaccharomyces; Spindle Pole Bodies
PubMed: 24112974
DOI: 10.1016/j.cub.2013.07.024 -
Philosophical Transactions of the Royal... Sep 2014The yeast spindle pole body (SPB) is the functional equivalent of the centrosome. Most SPB components have been identified and their functions partly established. This... (Review)
Review
The yeast spindle pole body (SPB) is the functional equivalent of the centrosome. Most SPB components have been identified and their functions partly established. This involved a large variety of techniques which are described here, and the potential use of some of these in the centrosome field is highlighted. In particular, very useful structural information on the SPB was obtained from a reconstituted complex, the γ-tubulin complex, and also from a sub-particle, SPB cores, prepared by extraction of an enriched SPB preparation. The labelling of SPB proteins with GFP at the N or C termini, using GFP tags inserted into the genome, gave informative electron microscopy localization and fluorescence resonance energy transfer data. Examples are given of more precise functional data obtained by removing domains from one SPB protein, Spc110p, without affecting its essential function. Finally, a structural model for SPB duplication is described and the differences between SPB and centrosome duplication discussed.
Topics: Calmodulin-Binding Proteins; Centrosome; Cytoskeletal Proteins; Fluorescence Resonance Energy Transfer; Green Fluorescent Proteins; Microscopy, Electron; Nuclear Proteins; Phenotype; Saccharomyces cerevisiae Proteins; Spindle Pole Bodies; Tubulin; Two-Hybrid System Techniques; Yeasts
PubMed: 25047610
DOI: 10.1098/rstb.2013.0456 -
Reproduction (Cambridge, England) Feb 2019Cells that divide during embryo development require precisely two centrioles during interphase and four centrioles during mitosis. This precise number is maintained by... (Review)
Review
Cells that divide during embryo development require precisely two centrioles during interphase and four centrioles during mitosis. This precise number is maintained by allowing each centriole to nucleate only one centriole per cell cycle (i.e. centriole duplication). Yet, how the first cell of the embryo, the zygote, obtains two centrioles has remained a mystery in most mammals and insects. The mystery arose because the female gamete (oocyte) is thought to have no functional centrioles and the male gamete (spermatozoon) is thought to have only one functional centriole, resulting in a zygote with a single centriole. However, recent studies in fruit flies, beetles and mammals, including humans, suggest an alternative explanation: spermatozoa have a typical centriole and an atypical centriole. The sperm typical centriole has a normal structure but distinct protein composition, whereas the sperm atypical centriole is distinct in both. During fertilization, the atypical centriole is released into the zygote, nucleates a new centriole and participates in spindle pole formation. Thus, the spermatozoa's atypical centriole acts as a second centriole in the zygote. Here, we review centriole biology in general and especially in reproduction, we describe the discovery of the spermatozoon atypical centriole, and we provide an updated model for centriole inherence during sexual reproduction. While we focus on humans and other non-rodent mammals, we also provide a broader evolutionary perspective.
Topics: Animals; Centrioles; Embryo, Mammalian; Embryonic Development; Female; Fertilization; Humans; Male; Mitosis; Oocytes; Spermatozoa
PubMed: 30496124
DOI: 10.1530/REP-18-0350