negative regulation of microtubule binding

Definition

Target type: biologicalprocess

Any process that stops, prevents or reduces the frequency, rate or extent of microtubule binding. [GO_REF:0000059, GOC:als, GOC:TermGenie, PMID:24520051]

Negative regulation of microtubule binding is a crucial cellular process that fine-tunes the dynamic assembly and disassembly of microtubules, essential cytoskeletal components involved in various cellular functions, including cell division, intracellular transport, and cell shape maintenance. This regulation ensures precise microtubule behavior and prevents uncontrolled polymerization or depolymerization.

Several mechanisms contribute to negative regulation of microtubule binding:

**1. Microtubule Depolymerizing Proteins:**
- **Katanin:** A protein complex that severs microtubules, effectively reducing their length and disrupting their stability.
- **Stathmin/Op18:** A protein that binds to tubulin dimers, the building blocks of microtubules, preventing their addition to growing microtubules. This inhibits microtubule polymerization and promotes depolymerization.
- **Kinases:** Certain kinases, such as CDK5 and GSK3β, can phosphorylate tubulin dimers or microtubule-associated proteins (MAPs), destabilizing microtubule structure and promoting depolymerization.

**2. Microtubule-Binding Proteins:**
- **Microtubule-associated proteins (MAPs):** Certain MAPs, like the tau protein, can bind to microtubules and promote their depolymerization by inducing conformational changes in the microtubule structure.
- **Microtubule-severing enzymes:** These enzymes, such as katanin and spastin, specifically cleave microtubules, effectively shortening them and reducing their stability.

**3. Molecular Chaperones:**
- **HSPs:** Heat shock proteins (HSPs) can interact with tubulin dimers and prevent their incorporation into microtubules, thereby inhibiting polymerization.

**4. Chemical Modification of Tubulin:**
- **Tyrosination/Detyrosination:** The presence or absence of a tyrosine residue at the C-terminus of α-tubulin can influence microtubule stability and interactions with MAPs.
- **Glycylation:** The addition of glycine residues to the C-terminus of α-tubulin can influence microtubule stability and dynamics.

**5. Regulation by Signaling Pathways:**
- **MAPK signaling:** The mitogen-activated protein kinase (MAPK) pathway can activate kinases that phosphorylate and regulate microtubule-associated proteins, influencing microtubule dynamics.
- **Ca2+ signaling:** Calcium ions (Ca2+) can activate calpains, proteases that can cleave MAPs, leading to microtubule destabilization.

These intricate regulatory mechanisms ensure that microtubules are appropriately assembled and disassembled in response to cellular needs, enabling diverse cellular functions and maintaining overall cellular integrity.'
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Proteins (1)

Compounds (1)