ESTeSL - Capítulos ou partes de livros
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Browsing ESTeSL - Capítulos ou partes de livros by contributor "Wawruszak, A."
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- Tubulin acetylation and the cellular mechanosensing and stress responsePublication . Carmona, Bruno; Delgado, Inês L. S.; Nolasco, Sofia; Marques, Rita; Gonçalves, João; Soares, Helena; Halasa, M.; Wawruszak, A.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. Furthermore, tubulin acetylation regulates intracellular trafficking by modulating interactions with molecular motors, allowing for efficient cargo transport and precise spatial organization without disrupting the MT network. In the context of oxidative stress, tubulin acetylation responds to redox imbalances by stabilizing MTs and influencing cellular pathways that regulate reactive oxygen species (ROS). This modification is linked to enhanced antioxidant responses, autophagy regulation, and mitochondrial dynamics, highlighting its role in maintaining cellular homeostasis under oxidative conditions. The dual function of tubulin acetylation, responding to and integrating signals from mechanical and oxidative stress, acts as a bridging mechanism between physical and chemical signaling pathways. Consequently, it has the potential to be a therapeutic target in diseases characterized by dysregulated stress responses, including neurodegenerative disorders, cancer, and cardiovascular conditions. Despite significant progress having been made, unanswered questions persist, particularly regarding the molecular mechanisms by which acetylated MTs encode spatial and functional information and their interplay with other tubulin PTMs.
- Tubulin acetylation: a critical regulator of microtubule functionPublication . Delgado, Inês L.; Carmona, Bruno; Nolasco, Sofia; Marques, Rita; Gonçalves, João; Soares, Helena; Halasa, M.; Wawruszak, A.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. One of the PTMs that has been extensively studied is the acetylation of lysine 40 (K40) on α-tubulin, which specifically occurs inside the MT lumen. Acetylation plays a crucial role in controlling the stability and function of MTs in response to signals from within and outside the cell. It impacts the cytoplasm's 3D arrangement and important cellular activities like intracellular transport, cell division, polarity, and migration. Recent research has also emphasized the significance of this PTM in regulating the mechanical properties of MTs and cellular sensing. The levels and activity of MT acetyltransferases and deacetylases are tightly regulated through various transcriptional, post-transcriptional, and post-translational mechanisms, including miRNAs, phosphorylation, protein-protein interactions, and regulated localization between the nucleus and cytoplasm. These regulatory processes involve components of diverse signaling pathways, and their deregulation has been implicated in numerous diseases, including neurological disorders, cancer, and cardiac conditions.