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Microtubules (MTs) are an essential component of the neuronal cytoskeleton; they are involved in various aspects of neuron development, maintenance, and functions including polarization, synaptic plasticity, and transport. Neuronal MTs are highly heterogeneous due to the presence of multiple tubulin isotypes and extensive post-translational modifications (PTMs). These PTMs-most notably detyrosination, acetylation, and polyglutamylation-have emerged as important regulators of the neuronal microtubule cytoskeleton. With this review, we summarize what is currently known about the impact of tubulin PTMs on microtubule dynamics, neuronal differentiation, plasticity, and transport as well as on brain function in normal and pathological conditions, in particular during neuro-degeneration. The main therapeutic approaches to neuro-diseases based on the modulation of tubulin PTMs are also summarized. Overall, the review indicates how tubulin PTMs can generate a large number of functionally specialized microtubule sub-networks, each of which is crucial to specific neuronal features.
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http://dx.doi.org/10.1002/dneu.22774 | DOI Listing |
bioRxiv
August 2025
Department of Cell & Developmental Biology, University of Michigan Medical School, Ann Arbor, MI, USA. 48109.
Microtubules are cytoskeletal filaments with critical roles in cell division, cell motility, intracellular trafficking, and cilium function. In cells, subsets of microtubules are selectively marked by posttranslational modifications (PTMs), which control the ability of microtubule-associated proteins (MAPs) and molecular motors to engage microtubules. Detyrosination (ΔY) and ΔC2 are PTMs of α-tubulin, wherein one or two residues, respectively, are enzymatically removed from the C-terminus of the protein.
View Article and Find Full Text PDFCytoskeleton (Hoboken)
July 2025
Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, Michigan, USA.
Microtubules play essential roles in numerous cellular processes. All microtubules are built from the protein tubulin, yet individual microtubules can differ spatially and temporally due to their tubulin isotype composition and post-translational modifications (PTMs). The tubulin code hypothesis posits that these differences can regulate microtubule function.
View Article and Find Full Text PDFCytoskeleton (Hoboken)
July 2025
Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
Post-translational modifications (PTMs) to tubulin subunits in microtubule filaments are thought to comprise a component of the tubulin code that specifies microtubule functions in cell physiology and animal development. Acetylation of Lysine-40 (K40) on α-tubulin (αTub-K40ac) and glutamylation of both α- and β-tubulin are two tubulin PTMs of interest to the field. Antibodies that recognize these PTMs have been indispensable tools to study the localization of these PTMs as well as their biological functions.
View Article and Find Full Text PDFResults Probl Cell Differ
July 2025
Centro de Química Estrutural, Institute of Molecular Sciences, Faculdade de Ciências, Universidade de Lisboa, Lisbon, Portugal.
Microtubule (MT) acetylation has emerged as a critical regulator of cellular stress responses, integrating mechanical and oxidative stimuli to support cellular adaptability and survival. This post-translational modification (PTM) enhances MT flexibility and resilience, enabling cells to withstand mechanical challenges such as changes in extracellular matrix stiffness and applied forces. Through its impact on MT physical properties, acetylation minimizes cytoskeletal breakage, reducing the need for constant remodeling and supporting cellular integrity under mechanical stress.
View Article and Find Full Text PDFResults Probl Cell Differ
July 2025
Centro de Química Estrutural, Institute of Molecular Sciences, Faculdade de Ciências, Universidade de Lisboa, Lisbon, Portugal.
The cytoskeleton is conserved throughout the eukaryotic lineage and consists of a complex dynamic network mainly composed of three distinct polymers: microtubules (MTs), actin filaments, and intermediate filaments. MTs are polymers of α/β-tubulin heterodimers, playing a myriad of distinct cellular functions and are the main components of complex structures like the mitotic spindle, cilia, and centrioles. Post-translational modifications (PTMs) regulate the function and increase the complexity of the α/β-tubulin heterodimer pools.
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