tubulin deacetylation

Definition

Target type: biologicalprocess

The removal of an acetyl group from tubulin. An acetyl group is CH3CO-, derived from acetic [ethanoic] acid. [GOC:BHF, GOC:dph, GOC:tb]

Tubulin deacetylation is a crucial post-translational modification that plays a significant role in regulating microtubule dynamics and cellular processes. It involves the removal of an acetyl group from the α-tubulin subunit, specifically at lysine 40 (K40) within the luminal domain. This deacetylation event is catalyzed by histone deacetylases (HDACs), particularly HDAC6, which possesses a unique catalytic domain that preferentially targets α-tubulin.

The process of tubulin deacetylation is tightly controlled and influenced by various factors, including cellular stress, microtubule stability, and the presence of specific proteins. In general, deacetylation promotes microtubule disassembly and destabilization. Deacetylated microtubules exhibit increased dynamics, resulting in faster depolymerization rates and reduced polymerization rates.

Several mechanisms contribute to the impact of deacetylation on microtubule dynamics:

1. **Binding affinity:** Deacetylation alters the binding affinity of α-tubulin for microtubule-associated proteins (MAPs). Deacetylated α-tubulin has reduced affinity for certain MAPs, like MAP2, leading to their dissociation from microtubules. This dissociation weakens microtubule stability and promotes depolymerization.

2. **Microtubule severing:** HDAC6, the primary deacetylase of α-tubulin, possesses a microtubule-binding domain and can directly interact with microtubules. This interaction facilitates microtubule severing, a process that breaks microtubules into shorter fragments and increases their dynamic instability.

3. **Microtubule depolymerization:** Deacetylated microtubules are more susceptible to depolymerization by factors like the kinesin-13 family of proteins, which act as microtubule depolymerases. This increased susceptibility further contributes to the destabilizing effect of deacetylation.

The biological significance of tubulin deacetylation extends beyond microtubule dynamics. It plays a crucial role in various cellular processes, including:

1. **Cell migration:** Deacetylation is essential for regulating cell migration by controlling the dynamics of microtubules, which provide tracks for motor proteins responsible for cell movement.

2. **Cell division:** During mitosis, tubulin deacetylation is critical for the proper formation and segregation of chromosomes. Deacetylation promotes microtubule disassembly at the spindle poles, facilitating chromosome separation.

3. **Protein trafficking:** Deacetylation influences the transport of proteins within the cell, as it affects the stability and dynamics of microtubules, which act as a network for protein trafficking.

4. **Neurogenesis:** In the nervous system, tubulin deacetylation plays a role in neuronal development and plasticity, impacting axonal growth and guidance.

5. **Stress response:** Deacetylation is also involved in cellular stress responses, as it can promote microtubule disassembly and facilitate the removal of damaged or misfolded proteins from cells.

Overall, tubulin deacetylation is a crucial regulatory mechanism that fine-tunes microtubule dynamics and cellular processes, influencing cell migration, division, protein trafficking, neuronal function, and the response to cellular stress.'
"

Proteins (2)

Compounds (135)