Tubulin Post-Translational Modifications: The Elusive Roles of Acetylation

Abstract

Microtubules (MTs), dynamic polymers of α/β-tubulin heterodimers found in all eukaryotes, are involved in cytoplasm spatial organization, intracellular transport, cell polarity, migration and division, and in cilia biology. MTs functional diversity depends on the differential expression of distinct tubulin isotypes and is amplified by a vast number of different post-translational modifications (PTMs). The addition/removal of PTMs to α- or β-tubulins is catalyzed by specific enzymes and allows combinatory patterns largely enriching the distinct biochemical and biophysical properties of MTs, creating a code read by distinct proteins, including microtubule-associated proteins (MAPs), which allow cellular responses. This review is focused on tubulin-acetylation, whose cellular roles continue to generate debate. We travel through the experimental data pointing to α-tubulin Lys40 acetylation role as being a MT stabilizer and a typical PTM of long lived MTs, to the most recent data, suggesting that Lys40 acetylation enhances MT flexibility and alters the mechanical properties of MTs, preventing MTs from mechanical aging characterized by structural damage. Additionally, we discuss the regulation of tubulin acetyltransferases/desacetylases and their impacts on cell physiology. Finally, we analyze how changes in MT acetylation levels have been found to be a general response to stress and how they are associated with several human pathologies.

HDAC6-dependent deacetylation of NGF dictates its ubiquitination and maintains primordial follicle dormancy

“…HDAC6 has been shown to promote α-tubulin (K40) (ac-Tubulin) acetylation levels 68 . The protein levels of ac-Tubulin were significantly decreased in ovaries, kidneys, lungs, and liver in Hdac6 -OE mice ( Figure S3 C-H).…”

Balancing Act: Tubulin Glutamylation and Microtubule Dynamics in Toxoplasma gondii

“…MTs can present varied dynamic properties and stability, which are influenced by factors such as the preferential incorporation of specific tubulin isotypes (products of different tubulin genes) and by tubulin PTMs such as acetylation, detyrosination, glutamylation, and glycylation [ 44 , 45 ]. Tubulin PTMs can selectively and reversibly affect distinct MT subpopulations [ 46 ].…”

“…For instance, α-tubulin can undergo acetylation at K40, which is the sole known PTM that localizes in the luminal surface of MTs [ 44 , 45 ]. Additionally, its C-terminal tail can undergo a reversible modification through the deletion of the terminal tyrosine (detyrosination) or an irreversible modification by deletion of the last two residues (Δ2).…”

“…Additionally, its C-terminal tail can undergo a reversible modification through the deletion of the terminal tyrosine (detyrosination) or an irreversible modification by deletion of the last two residues (Δ2). The C-terminal tails of both α- and β-tubulins can also be reversibly modified by glutamylation and glycylation [ 44 , 45 ]. While the K40 PTM has been linked to MT stability [ 47 ], C-terminal PTMs alter MT interactions with associated proteins, thereby influencing sensitivity to MT-targeting drugs.…”

Microtubule‐targeting agents for cancer treatment: Seven binding sites and three strategies

“…Microtubule dynamics is modulated by tubulin posttranslational modifications (e.g., acetylation, phosphorylation, and detyrosination), 21–24 and by the expression of diverse tubulin isotypes 25–27 . It is also tightly regulated through the coordination of microtubule‐associated proteins (MAPs) 28,29 .…”