Multifaceted roles of centrosomes in development, health, and disease

Qi, Feifei; Zhou, Jun

doi:10.1093/jmcb/mjab041

Cited by 20 publications

(15 citation statements)

References 135 publications

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“… 139 Therefore, it is not surprising that centrosome dysfunction is also closely associated with ciliopathy. 140 Moreover, primary cilia exist in hematopoietic cells and regulate the Hh signaling pathway. 141 Further, the number of primary cilia in AML cells decreases while the mutation frequency of primary cilia increases.…”

Section: Future Perspectivesmentioning

confidence: 99%

Centrosome Defects in Hematological Malignancies: Molecular Mechanisms and Therapeutic Insights

Wang

Zhou

2022

Blood Science

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Defects in centrosomes are associated with a broad spectrum of hematological malignancies, such as leukemia and lymphoma. Centrosomes in these malignancies display both numerical and structural aberrations, including alterations in the number and size of centrioles, inappropriate post-translational modification of centrosomal proteins, and extra centrosome clustering. There is accumulating evidence that centrosome defects observed in hematological malignancies result from multiple factors, including dysregulation of the centrosome cycle and impairment of centriole biogenesis. In this review, we discuss the plausible mechanisms of centrosome defects and highlight their consequences in hematological malignancies. We also illustrate the latest therapeutic strategies against hematological malignancies by targeting centrosome anomalies.

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Section: Future Perspectivesmentioning

confidence: 99%

Centrosome Defects in Hematological Malignancies: Molecular Mechanisms and Therapeutic Insights

Wang

Zhou

2022

Blood Science

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“…In multicellular organisms including humans, the centrosome plays a critical role in the regulation of development and tissue homeostasis, often through its cell type–specific functions (Tang & Marshall, 2012 ; Araújo, 2019 ; Bornens, 2021 ; Qi & Zhou, 2021 ). As a prime example, in the Drosophila larval neural stem cell or neuroblast (NB), which undergoes stereotypical asymmetric cell division (Gallaud et al , 2017 ), the centrosome regulates spindle orientation and division axis maintenance through a unconventional behaviour specific to this cell type (Rebollo et al , 2007 ; Rusan & Peifer, 2007 ).…”

Section: Introductionmentioning

confidence: 99%

APC/C‐dependent degradation of Spd2 regulates centrosome asymmetry in Drosophila neural stem cells

et al. 2023

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A functional centrosome is vital for the development and physiology of animals. Among numerous regulatory mechanisms of the centrosome, ubiquitin-mediated proteolysis is known to be critical for the precise regulation of centriole duplication. However, its significance beyond centrosome copy number control remains unclear. Using an in vitro screen for centrosomal substrates of the APC/C ubiquitin ligase in Drosophila, we identify several conserved pericentriolar material (PCM) components, including the inner PCM protein Spd2. We show that Spd2 levels are controlled by the interphase-specific form of APC/C, APC/C Fzr , in cultured cells and developing brains. Increased Spd2 levels compromise neural stem cell-specific asymmetric PCM recruitment and microtubule nucleation at interphase centrosomes, resulting in partial randomisation of the division axis and segregation patterns of the daughter centrosome in the following mitosis. We further provide evidence that APC/C Fzr -dependent Spd2 degradation restricts the amount and mobility of Spd2 at the daughter centrosome, thereby facilitating the accumulation of Polo-dependent Spd2 phosphorylation for PCM recruitment. Our study underpins the critical role of cell cycle-dependent proteolytic regulation of the PCM in stem cells.

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“…An association between large vacuoles and sperm chromatin immaturity has been demonstrated ( 24 ). Recently, the focus was oriented on the sperm centriolar region, since, in humans, sperm itself contributes centrioles to the zygote ( 25 , 26 ). Fishman et al ( 27 ), using electron microscopy with high pressure freezing, demonstrated that in mature human spermatozoa two centrioles are present, revising the centrosome reduction dogma ( 28 ).…”

Section: Sperm Morphology At Transmission Electron Microscopy Levelsmentioning

confidence: 99%

The relevance of sperm morphology in male infertility

Moretti

Signorini

Noto

et al. 2022

Front. Reprod. Health

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This brief report concerns the role of human sperm morphology assessment in different fields of male infertility: basic research, genetics, assisted reproduction technologies, oxidative stress. One of the best methods in studying sperm morphology is transmission electron microscopy (TEM) that enables defining the concept of sperm pathology and classifying alterations in non-systematic and systematic. Non-systematic sperm defects affect head and tail in variable ratio, whereas the rare systematic defects are characterized by a particular anomaly that marks most sperm of an ejaculate. TEM analysis and fluorescence in situ hybridization represent outstanding methods in the study of sperm morphology and cytogenetic in patients with altered karyotype characterizing their semen quality before intracytoplasmic sperm injection. In recent years, the genetic investigations on systematic sperm defects, made extraordinary progress identifying candidate genes whose mutations induce morphological sperm anomalies. The question if sperm morphology has an impact on assisted fertilization outcome is debated. Nowadays, oxidative stress represents one of the most important causes of altered sperm morphology and function and can be analyzed from two points of view: 1) spermatozoa with cytoplasmic residue produce reactive oxygen species, 2) the pathologies with inflammatory/oxidative stress background cause morphological alterations. Finally, sperm morphology is also considered an important endpoint in in vitro experiments where toxic substances, drugs, antioxidants are tested. We think that the field of sperm morphology is far from being exhausted and needs other research. This parameter can be still considered a valuable indicator of sperm dysfunction both in basic and clinical research.

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Multifaceted roles of centrosomes in development, health, and disease

Cited by 20 publications

References 135 publications

Centrosome Defects in Hematological Malignancies: Molecular Mechanisms and Therapeutic Insights

Centrosome Defects in Hematological Malignancies: Molecular Mechanisms and Therapeutic Insights

APC/C‐dependent degradation of Spd2 regulates centrosome asymmetry in Drosophila neural stem cells

The relevance of sperm morphology in male infertility

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