Causes and Consequences of Microtubule Acetylation

Abstract

Among the different types of cytoskeletal components, microtubules arguably accumulate the greatest diversity of post-translational modifications (PTMs). Acetylation of lysine 40 (K40) of α-tubulin has received particular attention because it is the only tubulin PTM to be found in the lumen of microtubules: most other tubulin PTMs are found at the outer surface of the microtubule. As a consequence, the enzyme catalyzing K40 acetylation needs to penetrate the narrow microtubule lumen to find its substrate. Acetylated microtubules have been considered to be stable, long-lived microtubules; however, until recently, there was little information about whether the longevity of these microtubules is the cause or the consequence of acetylation. Current advances suggest that this PTM helps the microtubule lattice to cope with mechanical stress, thus facilitating microtubule self-repair. These observations now shed new light on the structural integrity of microtubules, as well as on the mechanisms and biological functions of tubulin acetylation. Here, we discuss recent insights into how acetylation is generated in the lumen of microtubules, and how this 'hidden' PTM can control the properties and functions of microtubules.

SMIFH2 inhibition of platelets demonstrates a critical role for formin proteins in platelet cytoskeletal dynamics

“…Tubulin PTMs have been shown to be important in regulating both microtubule stability and their interaction with microtubule associated proteins and are part of a tubulin code that regulates cytoskeletal dynamics. 32,35,36 Furthermore, tubulin PTMs, including acetylation, polyglutamylation, and polyglycylation have been shown to be important in platelets and megakaryocytes. 37,38 The changes reported here could affect the platelet microtubule coil in a number of ways: (a) tubulin acetylation is associated with the protection of microtubules from mechanical stress, 36 (b) increased tyrosination is associated with more dynamic microtubules 39 , and (c) increased tyrosination is associated with increased kinesin motor activity.…”

Key Role of Microtubule and Its Acetylation in a Zinc Oxide Nanoparticle–Mediated Lysosome–Autophagy System

“…Acetylated MTs have attracted attention because they are the only post‐translationally modified tubulin that can be found in the MT lumen. MT acetylation increases with the accumulation of MT defects . Interestingly, ZNPs increased the level of acetylated MTs at the early stage (≤3 h) and then decreased it to the basal level at the late stage (≥6 h) (Figure F–H).…”

“…MTs are among the main cytoskeletal components . Although it has been reported that the MT system does not directly participate in the autophagy process under basal conditions, the opposite has also been stated, especially in stress‐induced autophagy .…”

“…MTs are among the main cytoskeletal components. [42] Although it has been reported that the MT system does not directly participate in the autophagy process under basal conditions, [52] the opposite has also been stated, especially in stressinduced autophagy. [14] For example, MT disruption decreased the formation of mature autophagosomes, [52,53] though it is still controversial whether intact MT is essential for fusion between autophagosomes and lysosomes.…”

“…MT acetylation increases with the accumulation of MT defects. [42] Interestingly, ZNPs increased the level of acetylated MTs at the early stage (≤3 h) and then decreased it to the basal level at the late stage (≥6 h) ( Figure 6F-H). This increase in acetylated MTs at the early stage may have been due to MT defects occurring as early as 1 h. Additionally, even acetylated MTs was observed at 1 h, a frequent decrease in acetylated MTs was observed after Zn 2+ sequestration via EDTA at the late stage (≥3 h) ( Figure 6F).…”