Although compelling evidence has been obtained for heterogeneity in the structure of subunits in microtubules, it has not been possible to prove that this results from the presence of tubulin-GDP and tubulin-GTP in polymers. There are reasons to exclude the existence of even a monolayer of tubulin-GTP subunits at microtubule ends. Dynamic behavior appears to be best accounted for by a mechanism in which tubulin-GDP in microtubules exists in two conformations. The mechanism of microtubule-associated protein binding to microtubules and the role of phosphorylation on this reaction are discussed.
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http://dx.doi.org/10.1016/0955-0674(92)90059-l | DOI Listing |
Unlabelled: Melanin pigments block genotoxic agents by positioning on the sun-exposed side of human skin keratinocytes' nucleus. How this position is regulated and its role in genome photoprotection remains unknown. By developing a model of human keratinocytes internalizing extracellular melanin into pigment organelles, we show that keratin 5/14 intermediate filaments mechanically control the 3D perinuclear position of pigments, shielding DNA from photodamage.
View Article and Find Full Text PDFDev Biol
January 2025
Aix Marseille Univ, CNRS, IBDM, Turing Centre for Living Systems, Marseille, France. Electronic address:
In developing tissues, the number, position, and differentiation of cells must be coordinately controlled to ensure the emergence of physiological function. The epidermis of the Xenopus embryo contains thousands of uniformly distributed multiciliated cells (MCCs), which grow hundreds of coordinately polarized cilia that beat vigorously to generate superficial water flow. Using this model, we uncovered a dual role for the conserved centriolar component Odf2, in MCC apical organization at the cell level, and in MCC spatial distribution at the tissue level.
View Article and Find Full Text PDFCurr Opin Neurobiol
January 2025
Department of Pathology & Cell Biology, Columbia University Irving Medical Center, 10032, New York, NY, USA. Electronic address:
Neurons are equipped with microtubules of different stability with stable and dynamic domains often coexisting on the same microtubule. While dynamic microtubules undergo random transitions between disassembly and assembly, stable ones persist long enough to serve as platforms for tubulin-modifying enzymes (known as writers) that attach molecular components to the α- or β-tubulin subunits. The combination of these posttranslational modifications (PTMs) results in a "tubulin code," dictating the behavior of selected proteins (known as readers), some of which were shown to be crucial for neuronal function.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
Division of Biomedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, 300 Prince Philip Drive, St. Johns, NL A1B 3V6, Canada.
Cell immortalization corresponds to a biologically relevant clinical feature that allows cells to acquire a high proliferative potential during carcinogenesis. In multiple cancer types, Protein Kinase D3 (PKD3) has often been reported as a dysregulated oncogenic kinase that promotes cell proliferation. Using mouse embryonic fibroblasts (MEFs), in a spontaneous immortalization model, PKD3 has been demonstrated as a critical regulator of cell proliferation after immortalization.
View Article and Find Full Text PDFNat Struct Mol Biol
January 2025
Cell Biology, Neurobiology and Biophysics, Department of Biology, Faculty of Science, Utrecht University, Utrecht, The Netherlands.
Cilia are motile or sensory organelles present on many eukaryotic cells. Their formation and function rely on axonemal microtubules, which exhibit very slow dynamics, but the underlying mechanisms are largely unexplored. Here we reconstituted in vitro the individual and collective activities of the ciliary tip module proteins CEP104, CSPP1, TOGARAM1, ARMC9 and CCDC66, which interact with each other and with microtubules and, when mutated in humans, cause ciliopathies such as Joubert syndrome.
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