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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 -
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 -
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 -
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 -
Centrosome linker diversity and its function in centrosome clustering and mitotic spindle formation.The EMBO Journal Sep 2023The centrosome linker joins the two interphase centrosomes of a cell into one microtubule organizing center. Despite increasing knowledge on linker components, linker...
The centrosome linker joins the two interphase centrosomes of a cell into one microtubule organizing center. Despite increasing knowledge on linker components, linker diversity in different cell types and their role in cells with supernumerary centrosomes remained unexplored. Here, we identified Ninein as a C-Nap1-anchored centrosome linker component that provides linker function in RPE1 cells while in HCT116 and U2OS cells, Ninein and Rootletin link centrosomes together. In interphase, overamplified centrosomes use the linker for centrosome clustering, where Rootletin gains centrosome linker function in RPE1 cells. Surprisingly, in cells with centrosome overamplification, C-Nap1 loss prolongs metaphase through persistent activation of the spindle assembly checkpoint indicated by BUB1 and MAD1 accumulation at kinetochores. In cells lacking C-Nap1, the reduction of microtubule nucleation at centrosomes and the delay in nuclear envelop rupture in prophase probably cause mitotic defects like multipolar spindle formation and chromosome mis-segregation. These defects are enhanced when the kinesin HSET, which normally clusters multiple centrosomes in mitosis, is partially inhibited indicating a functional interplay between C-Nap1 and centrosome clustering in mitosis.
Topics: Centrosome; Cell Cycle; Cell Cycle Proteins; Interphase; Mitosis; Spindle Apparatus
PubMed: 37401899
DOI: 10.15252/embj.2021109738 -
Frontiers in Endocrinology 2020The centrosome apparatus is vital for spindle assembly and chromosome segregation during mitotic divisions. Its replication, disjunction and separation have to be... (Review)
Review
The centrosome apparatus is vital for spindle assembly and chromosome segregation during mitotic divisions. Its replication, disjunction and separation have to be fine-tuned in space and time. A multitude of post-translational modifications (PTMs) have been implicated in centrosome modulation, including phosphorylation, ubiquitination and acetylation. Among them is the emerging O-linked N-acetylglucosamine (O-GlcNAc) modification. This quintessential PTM has a sole writer, O-GlcNAc transferase (OGT), and the only eraser, O-GlcNAcase (OGA). O-GlcNAc couples glucose metabolism with signal transduction and forms a yin-yang relationship with phosphorylation. Evidence from proteomic studies as well as single protein investigations has pinpointed a role of O-GlcNAc in centrosome number and separation, centriole number and distribution, as well as the cilia machinery emanating from the centrosomes. Herein we review our current understanding of the sweet modification embedded in centrosome dynamics and speculate that more molecular details will be unveiled in the future.
Topics: Acetylglucosamine; Animals; Centrosome; Cilia; Humans; N-Acetylglucosaminyltransferases
PubMed: 33597927
DOI: 10.3389/fendo.2020.621888 -
Open Biology Oct 2022The centrosome, consisting of centrioles and the associated pericentriolar material, is the main microtubule-organizing centre (MTOC) in animal cells. During most of... (Review)
Review
The centrosome, consisting of centrioles and the associated pericentriolar material, is the main microtubule-organizing centre (MTOC) in animal cells. During most of interphase, the two centrosomes of a cell are joined together by centrosome cohesion into one MTOC. The most dominant element of centrosome cohesion is the centrosome linker, an interdigitating, fibrous network formed by the protein C-Nap1 anchoring a number of coiled-coil proteins including rootletin to the proximal end of centrioles. Alternatively, centrosomes can be kept together by the action of the minus end directed kinesin motor protein KIFC3 that works on interdigitating microtubules organized by both centrosomes and probably by the actin network. Although cells connect the two interphase centrosomes by several mechanisms into one MTOC, the general importance of centrosome cohesion, particularly for an organism, is still largely unclear. In this article, we review the functions of the centrosome linker and discuss how centrosome cohesion defects can lead to diseases.
Topics: Animals; Kinesins; Actins; Protein C; NIMA-Related Kinases; Centrosome; Centrioles; Microtubules
PubMed: 36285440
DOI: 10.1098/rsob.220229 -
Current Opinion in Cell Biology Feb 2013Centrioles are the key foundation of centrosomes and cilia, yet a molecular understanding of how they form has only recently begun to emerge. Building a fully functional... (Review)
Review
Centrioles are the key foundation of centrosomes and cilia, yet a molecular understanding of how they form has only recently begun to emerge. Building a fully functional centriole that can form a centrosome and cilium requires two cell cycles. Centriole building starts with procentriole nucleation, a process that is coordinated by the conserved proteins Plk4/Zyg-1, and Asterless/Cep152. Subsequently, Sas-6, a conserved procentriole protein, self-assembles to provide nine-fold symmetry to the centriole scaffold. The procentriole then continues to elongate into a centriole, a process controlled by Sas-4/CPAP and CP110. Then, centrioles recruit Sas-4-mediated pre-assembled centrosomal complexes from the cytoplasm to form the pericentriolar material (PCM). Finally, CP110 and its interacting proteins are involved in controlling the timing of centriole templating of the cilium.
Topics: Animals; Cell Cycle; Centrioles; Cilia; Humans
PubMed: 23199753
DOI: 10.1016/j.ceb.2012.10.016 -
Cells Jul 2019Centrosomes and primary cilia are usually considered as distinct organelles, although both are assembled with the same evolutionary conserved, microtubule-based... (Review)
Review
Centrosomes and primary cilia are usually considered as distinct organelles, although both are assembled with the same evolutionary conserved, microtubule-based templates, the centrioles. Centrosomes serve as major microtubule- and actin cytoskeleton-organizing centers and are involved in a variety of intracellular processes, whereas primary cilia receive and transduce environmental signals to elicit cellular and organismal responses. Understanding the functional relationship between centrosomes and primary cilia is important because defects in both structures have been implicated in various diseases, including cancer. Here, we discuss evidence that the animal centrosome evolved, with the transition to complex multicellularity, as a hybrid organelle comprised of the two distinct, but intertwined, structural-functional modules: the centriole/primary cilium module and the pericentriolar material/centrosome module. The evolution of the former module may have been caused by the expanding cellular diversification and intercommunication, whereas that of the latter module may have been driven by the increasing complexity of mitosis and the requirement for maintaining cell polarity, individuation, and adhesion. Through its unique ability to serve both as a plasma membrane-associated primary cilium organizer and a juxtanuclear microtubule-organizing center, the animal centrosome has become an ideal integrator of extracellular and intracellular signals with the cytoskeleton and a switch between the non-cell autonomous and the cell-autonomous signaling modes. In light of this hypothesis, we discuss centrosome dynamics during cell proliferation, migration, and differentiation and propose a model of centrosome-driven microtubule assembly in mitotic and interphase cells. In addition, we outline the evolutionary benefits of the animal centrosome and highlight the hierarchy and modularity of the centrosome biogenesis networks.
Topics: Animals; Cell Cycle; Cell Differentiation; Centrioles; Centrosome; Cilia; Humans; Microtubule-Organizing Center; Microtubules; Mitosis; Organelles
PubMed: 31295970
DOI: 10.3390/cells8070701 -
Annual Review of Cell and Developmental... Oct 2021The purpose of this review is to explore self-organizing mechanisms that pattern microtubules (MTs) and spatially organize animal cell cytoplasm, inspired by recent... (Review)
Review
The purpose of this review is to explore self-organizing mechanisms that pattern microtubules (MTs) and spatially organize animal cell cytoplasm, inspired by recent experiments in frog egg extract. We start by reviewing conceptual distinctions between self-organizing and templating mechanisms for subcellular organization. We then discuss self-organizing mechanisms that generate radial MT arrays and cell centers in the absence of centrosomes. These include autocatalytic MT nucleation, transport of minus ends, and nucleation from organelles such as melanosomes and Golgi vesicles that are also dynein cargoes. We then discuss mechanisms that partition the cytoplasm in syncytia, in which multiple nuclei share a common cytoplasm, starting with cytokinesis, when all metazoan cells are transiently syncytial. The cytoplasm of frog eggs is partitioned prior to cytokinesis by two self-organizing modules, protein regulator of cytokinesis 1 (PRC1)-kinesin family member 4A (KIF4A) and chromosome passenger complex (CPC)-KIF20A. Similar modules may partition longer-lasting syncytia, such as early embryos. We end by discussing shared mechanisms and principles for the MT-based self-organization of cellular units.
Topics: Animals; Centrosome; Cytokinesis; Cytoskeleton; Golgi Apparatus; Microtubules
PubMed: 34186005
DOI: 10.1146/annurev-cellbio-120319-025356