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The conserved process of centriole duplication requires establishment of a Sas6-centred cartwheel initiated by Plk4's phosphorylation of Ana1/STIL. Subsequently the centriole undergoes conversion to a centrosome requiring its radial expansion and elongation, mediated by a network requiring interactions between Cep135, Ana1/Cep295, and Asterless/Cep152. Here we show that mutant alleles encoding overlapping N- and C-terminal parts of Ana1 are capable of intragenic complementation to rescue radial expansion. This permits recruitment of Asl and thereby centriole duplication and mechanosensory cilia formation to restore the coordination defects of these mutants. This genetic combination also rescues centriole duplication in the male germ line but does not rescue the elongation of the triplet microtubule-containing centrioles of primary spermatocytes and consequently these males are coordinated but sterile. Such centriole elongation is rescued by the continuous, full-length Ana1 sequence. We define a region that when deleted within otherwise intact Ana1 does not permit primary spermatocyte centrioles to elongate but still allows recruitment of Asl. Our findings point to differing demands upon the physical organization of Ana1 for the distinct processes of radial expansion and elongation of centrioles.
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http://dx.doi.org/10.1101/2024.10.28.620588 | DOI Listing |
Nat Commun
September 2025
Department of Physiological Chemistry, Graduate School of Pharmaceutical Science, The University of Tokyo, Bunkyo, Tokyo, Japan.
Copy number control of DNA and centrosomes is essential for accurate genetic inheritance. DNA replication and centrosome duplication have been recognized as parallel key events for cell division. Here, we discover that the DNA replication machinery directly regulates the licensing and execution processes of centrosome duplication to prevent centrosome amplification.
View Article and Find Full Text PDFCytoskeleton (Hoboken)
September 2025
Department of Genetics and Cell Biology, College of Life Sciences, State Key Laboratory of Medicinal Chemical Biology, Tianjin Union Medical Center, the First Affiliated Hospital of Nankai University, Nankai University, Tianjin, China.
The centrosomal protein of 44 kDa (CEP44) is essential for centriole duplication, centrosome cohesion, and spindle integrity. It localizes to the proximal end of centrioles and associates with spindle microtubules. Liquid-liquid phase separation (LLPS) is a process by which biomolecules undergo demixing into distinct liquid-like phases, facilitating the formation of cellular condensates such as the centrosome.
View Article and Find Full Text PDFCytoskeleton (Hoboken)
July 2025
Kusuma School of Biological Sciences, Indian Institute of Technology Delhi, New Delhi, India.
Optineurin (OPTN), a multifunctional cytosolic protein, is recognized as an autophagy adaptor. Its association with neurodegenerative diseases, like ALS, triggered extensive research. OPTN has been found in intracellular organelles, including the mitochondria, Golgi body, endosomes, microtubules, and the nucleus.
View Article and Find Full Text PDFCell Signal
August 2025
Department of Endocrine, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650101, China. Electronic address:
Background: Mitochondrial dysfunction is a major mechanism in the development of diabetic cardiomyopathy (DCM). However, the exact pathogenesis remains unclear, resulting in a lack of targeted clinical therapies. The aim of this study is to elucidate the mechanism by which ANXA11 affects DCM by inducing mitochondrial dysfunction through β-hydroxybutyrylation (kbhb).
View Article and Find Full Text PDFbioRxiv
July 2025
Department of Cell and Developmental Biology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
DNA damage can result from external sources or occur during programmed genome rearrangements in processes like immunity or meiosis. To maintain genome integrity, cells activate DNA repair pathways that prevent harmful outcomes such as cancer or immune dysfunction. In this study, we uncover a novel role for DNA damage during the terminal differentiation of multiciliated cells (MCCs).
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