Centrosome duplication occurs once per cell cycle and ensures that the two resulting centrosomes assemble a bipolar mitotic spindle. Centriole formation is fundamental for centrosome duplication. In Caenorhabditis elegans, the evolutionarily conserved proteins SPD-2, ZYG-1, SAS-6, SAS-5, and SAS-4 are essential for centriole formation, but how they function is not fully understood. Here, we demonstrate that Protein Phosphatase 2A (PP2A) is also critical for centriole formation in C. elegans embryos. We find that PP2A subunits genetically and physically interact with the SAS-5/SAS-6 complex. Furthermore, we show that PP2A-mediated dephosphorylation promotes centriolar targeting of SAS-5 and ensures SAS-6 delivery to the site of centriole assembly. We find that PP2A is similarly needed for the presence of HsSAS-6 at centrioles and for centriole formation in human cells. These findings lead us to propose that PP2A-mediated loading of SAS-6 proteins is critical at the onset of centriole formation.
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http://dx.doi.org/10.1016/j.devcel.2011.02.005 | DOI Listing |
Cell Rep
December 2024
State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, Jiangsu, China; Cellular Screening Center, The University of Chicago, Chicago, IL, USA; Department of Neurology, Center for Reproductive Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. Electronic address:
In male animals, spermatogonia in testes differentiate into sperm, one of the most diverse cell types across species. Despite the evolutionary retention of key genes essential for spermatogenesis, the extent of their conservation remains unclear. To explore the genetic basis of spermatogenesis under strong selective pressure, we compare single-cell RNA sequencing (scRNA-seq) datasets from the testes of humans, mice, and fruit flies.
View Article and Find Full Text PDFFront Biosci (Landmark Ed)
November 2024
Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, 230022 Hefei, Anhui, China.
Background: Aneuploidy is crucial yet under-explored in cancer pathogenesis. Specifically, the involvement of brain expressed X-linked gene 4 () in microtubule formation has been identified as a potential aneuploidy mechanism. Nevertheless, 's comprehensive impact on aneuploidy incidence across different cancer types remains unexplored.
View Article and Find Full Text PDFCurr Oncol
December 2024
Department of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan.
STIL is a regulatory protein essential for centriole biogenesis, and its dysregulation has been implicated in various diseases, including malignancies. However, its role in non-small-cell lung carcinoma (NSCLC) remains unclear. In this study, we examined STIL expression and its potential association with chromosomal numerical abnormalities (CNAs) in NSCLC using The Cancer Genome Atlas (TCGA) dataset, immunohistochemical analysis, and in vitro experiments with NSCLC cell lines designed to overexpress STIL.
View Article and Find Full Text PDFDev Cell
December 2024
Structural and Computational Biology Unit, European Molecular Biology Laboratory (EMBL), 69117 Heidelberg, Germany; Cell Biology and Biophysics Unit, EMBL, 69117 Heidelberg, Germany. Electronic address:
Centrosomes organize microtubules that are essential for mitotic divisions in animal cells. They consist of centrioles surrounded by pericentriolar material (PCM). Questions related to mechanisms of centriole assembly, PCM organization, and spindle microtubule formation remain unanswered, partly due to limited availability of molecular-resolution structural data inside cells.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
December 2024
Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390.
Brain neurons utilize the primary cilium as a privileged compartment to detect and respond to extracellular ligands such as Sonic hedgehog (SHH). However, cilia in cerebellar granule cell (GC) neurons disassemble during differentiation through ultrastructurally unique intermediates, a process we refer to as cilia deconstruction. In addition, mature neurons do not reciliate despite having docked centrioles.
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