negative regulation of microtubule polymerization or depolymerization

Definition

Target type: biologicalprocess

Any process that stops, prevents, or reduces the frequency, rate or extent of microtubule polymerization or depolymerization. [GOC:mah]

Microtubule polymerization and depolymerization are fundamental processes that govern the dynamic structure and function of microtubules, essential cytoskeletal elements involved in cell division, intracellular transport, and cell shape maintenance. Negative regulation of these processes involves mechanisms that inhibit microtubule assembly or promote disassembly, ensuring proper microtubule dynamics and preventing uncontrolled growth or disassembly.

**Mechanisms of Negative Regulation:**

**1. Microtubule Depolymerizing Proteins:**

* **Katanin:** This protein severs microtubules, promoting depolymerization and reducing microtubule length.
* **Stathmin/Op18:** This protein binds to tubulin dimers, preventing their addition to microtubule ends and promoting depolymerization.
* **Kinesin-13 family:** These motor proteins depolymerize microtubules by promoting the removal of tubulin subunits from the plus end.

**2. Microtubule-Binding Proteins:**

* **Tau:** This protein stabilizes microtubules, but high levels of tau can promote microtubule aggregation and destabilization, leading to neurodegenerative diseases.
* **MAP2:** Similar to tau, MAP2 can stabilize microtubules, but its binding can also promote depolymerization in certain contexts.

**3. Small Molecules and Drugs:**

* **Colchicine:** This drug binds to tubulin dimers and prevents their assembly into microtubules.
* **Vinblastine and Vincristine:** These drugs bind to tubulin dimers and promote the formation of aggregates, inhibiting microtubule polymerization.

**4. Post-Translational Modifications:**

* **Phosphorylation:** Phosphorylation of tubulin or microtubule-associated proteins can influence their assembly properties and promote depolymerization.
* **Acetylation:** Acetylation of tubulin can stabilize microtubules, but it can also contribute to depolymerization in specific cellular contexts.

**5. Cellular Environment:**

* **pH:** Changes in pH can affect microtubule stability and promote depolymerization.
* **Temperature:** Elevated temperatures can destabilize microtubules and promote depolymerization.

**Significance of Negative Regulation:**

Negative regulation of microtubule polymerization and depolymerization is crucial for maintaining proper microtubule dynamics and cellular function. This regulation ensures:

* **Accurate chromosome segregation during cell division:** By controlling microtubule assembly and disassembly, cells can ensure accurate chromosome segregation.
* **Efficient intracellular transport:** Dynamic microtubules act as tracks for motor proteins that transport vesicles and organelles. Negative regulation ensures efficient transport by controlling the availability of microtubules.
* **Cell shape and migration:** Microtubule dynamics are involved in shaping the cell and enabling cell migration. Negative regulation helps maintain cell shape and migration.

Dysregulation of microtubule polymerization and depolymerization can lead to various cellular malfunctions, including developmental defects, neurodegenerative diseases, and cancer.
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Proteins (1)

Compounds (7)