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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 -
Science (New York, N.Y.) Jun 2019Mammalian oocytes segregate chromosomes with a microtubule spindle that lacks centrosomes, but the mechanisms by which acentrosomal spindles are organized and function...
Mammalian oocytes segregate chromosomes with a microtubule spindle that lacks centrosomes, but the mechanisms by which acentrosomal spindles are organized and function are largely unclear. In this study, we identify a conserved subcellular structure in mammalian oocytes that forms by phase separation. This structure, which we term the liquid-like meiotic spindle domain (LISD), permeates the spindle poles and forms dynamic protrusions that extend well beyond the spindle. The LISD selectively concentrates multiple microtubule regulatory factors and allows them to diffuse rapidly within the spindle volume. Disruption of the LISD via different means disperses these factors and leads to severe spindle assembly defects. Our data suggest a model whereby the LISD promotes meiotic spindle assembly by serving as a reservoir that sequesters and mobilizes microtubule regulatory factors in proximity to spindle microtubules.
Topics: Animals; Aurora Kinase A; Centrosome; Clathrin Heavy Chains; Female; Fetal Proteins; Meiosis; Mice; Mice, Inbred C57BL; Microtubule-Associated Proteins; Microtubules; NIH 3T3 Cells; Oocytes; Spindle Apparatus
PubMed: 31249032
DOI: 10.1126/science.aat9557 -
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 -
Current Opinion in Structural Biology Feb 2021Centrioles are microtubule-based structures involved in cell division and ciliogenesis. Centriole formation is a highly regulated cellular process and aberrations in... (Review)
Review
Centrioles are microtubule-based structures involved in cell division and ciliogenesis. Centriole formation is a highly regulated cellular process and aberrations in centriole structure, size or numbers have implications in multiple human pathologies. In this review, we propose that the proteins that control centriole length can be subdivided into two classes based on their antagonistic activities on centriolar microtubules, which we refer to as 'centriole elongation activators' (CEAs) and 'centriole elongation inhibitors' (CEIs). We discuss and illustrate the structure-function relationship of CEAs and CEIs as well as their interaction networks. Based on our current knowledge, we formulate some outstanding open questions in the field and present possible routes for future studies.
Topics: Cell Cycle; Cell Cycle Proteins; Centrioles; Humans; Microtubules; Proteins
PubMed: 33220554
DOI: 10.1016/j.sbi.2020.10.011 -
The Journal of Cell Biology Apr 2024Centrosomes are the primary microtubule organizer in eukaryotic cells. In addition to shaping the intracellular microtubule network and the mitotic spindle, centrosomes... (Review)
Review
Centrosomes are the primary microtubule organizer in eukaryotic cells. In addition to shaping the intracellular microtubule network and the mitotic spindle, centrosomes are responsible for positioning cilia and flagella. To fulfill these diverse functions, centrosomes must be properly located within cells, which requires that they undergo intracellular transport. Importantly, centrosome mispositioning has been linked to ciliopathies, cancer, and infertility. The mechanisms by which centrosomes migrate are diverse and context dependent. In many cells, centrosomes move via indirect motor transport, whereby centrosomal microtubules engage anchored motor proteins that exert forces on those microtubules, resulting in centrosome movement. However, in some cases, centrosomes move via direct motor transport, whereby the centrosome or centriole functions as cargo that directly binds molecular motors which then walk on stationary microtubules. In this review, we summarize the mechanisms of centrosome motility and the consequences of centrosome mispositioning and identify key questions that remain to be addressed.
Topics: Biological Transport; Centrioles; Centrosome; Microtubules; Spindle Apparatus; Cilia; Humans; Animals; Dyneins
PubMed: 38512059
DOI: 10.1083/jcb.202311140 -
Cells Oct 2021The centrosome of amoebae contains no centrioles and consists of a cylindrical layered core structure surrounded by a corona harboring microtubule-nucleating γ-tubulin... (Review)
Review
The centrosome of amoebae contains no centrioles and consists of a cylindrical layered core structure surrounded by a corona harboring microtubule-nucleating γ-tubulin complexes. It is the major centrosomal model beyond animals and yeasts. Proteomics, protein interaction studies by BioID and superresolution microscopy methods led to considerable progress in our understanding of the composition, structure and function of this centrosome type. We discuss all currently known components of the centrosome in comparison to other centrosomes of animals and yeasts.
Topics: Cell Nucleus; Centrosome; Dictyostelium; Spindle Apparatus
PubMed: 34685637
DOI: 10.3390/cells10102657 -
Molecular and Cellular Endocrinology Dec 2020Centrioles are eukaryotic subcellular structures that produce and regulate massive cytoskeleton superstructures. They form centrosomes and cilia, regulate new centriole... (Review)
Review
Centrioles are eukaryotic subcellular structures that produce and regulate massive cytoskeleton superstructures. They form centrosomes and cilia, regulate new centriole formation, anchor cilia to the cell, and regulate cilia function. These basic centriolar functions are executed in sperm cells during their amplification from spermatogonial stem cells during their differentiation to spermatozoa, and finally, after fertilization, when the sperm fuses with the egg. However, sperm centrioles exhibit many unique characteristics not commonly observed in other cell types, including structural remodeling, centriole-flagellum transition zone migration, and cell membrane association during meiosis. Here, we discuss five roles of sperm centrioles: orchestrating early spermatogenic cell divisions, forming the spermatozoon flagella, linking the spermatozoon head and tail, controlling sperm tail beating, and organizing the cytoskeleton of the zygote post-fertilization. We present the historic discovery of the centriole as a sperm factor that initiates embryogenesis, and recent genetic studies in humans and other mammals evaluating the current evidence for the five functions of sperm centrioles. We also examine information connecting the various sperm centriole functions to distinct clinical phenotypes. The emerging picture is that centrioles are essential sperm components with remarkable functional diversity and specialization that will require extensive and in-depth future studies.
Topics: Animals; Cell Differentiation; Centrioles; Embryonic Development; Fertilization; Humans; Male; Meiosis; Spermatozoa
PubMed: 32810575
DOI: 10.1016/j.mce.2020.110987 -
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 -
Biology Dec 2016Anaphase B spindle elongation is characterized by the sliding apart of overlapping antiparallel interpolar (ip) microtubules (MTs) as the two opposite spindle poles... (Review)
Review
Anaphase B spindle elongation is characterized by the sliding apart of overlapping antiparallel interpolar (ip) microtubules (MTs) as the two opposite spindle poles separate, pulling along disjoined sister chromatids, thereby contributing to chromosome segregation and the propagation of all cellular life. The major biochemical "modules" that cooperate to mediate pole-pole separation include: (i) midzone pushing or (ii) braking by MT crosslinkers, such as kinesin-5 motors, which facilitate or restrict the outward sliding of antiparallel interpolar MTs (ipMTs); (iii) cortical pulling by disassembling astral MTs (aMTs) and/or dynein motors that pull aMTs outwards; (iv) ipMT plus end dynamics, notably net polymerization; and (v) ipMT minus end depolymerization manifest as poleward flux. The differential combination of these modules in different cell types produces diversity in the anaphase B mechanism. Combinations of antagonist modules can create a force balance that maintains the dynamic pre-anaphase B spindle at constant length. Tipping such a force balance at anaphase B onset can initiate and control the rate of spindle elongation. The activities of the basic motor filament components of the anaphase B machinery are controlled by a network of non-motor MT-associated proteins (MAPs), for example the key MT cross-linker, Ase1p/PRC1, and various cell-cycle kinases, phosphatases, and proteases. This review focuses on the molecular mechanisms of anaphase B spindle elongation in eukaryotic cells and briefly mentions bacterial DNA segregation systems that operate by spindle elongation.
PubMed: 27941648
DOI: 10.3390/biology5040051 -
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