U01.01.026 Microtubule

Microtubules are essential components of the cytoskeleton, acting like a cellular scaffolding system. Here’s a detailed breakdown of their structure, function, and interaction with motor proteins:

Structure:

Cylindrical, hollow tubes composed of:
- Heterodimers: Building blocks formed by two protein subunits, alpha-tubulin and beta-tubulin, bound together.
- Protofilaments: 13 linear protofilaments arranged in a spiral (helical array) to form the microtubule wall.
- GTP: Each tubulin subunit binds two GTP (guanosine triphosphate) molecules, which play a role in microtubule dynamics.

Function:

Maintaining Cell Shape: Microtubules help determine cell shape and rigidity.
Intracellular Transport: They act as tracks for motor proteins that transport organelles and vesicles throughout the cell.
Cell Division: Microtubules form the mitotic spindle, a structure that separates chromosomes during cell division.
Cilia and Flagella: These hair-like structures on the cell surface are composed of microtubules and enable movement of fluids or cell propulsion.
Axonal Transport: In neurons, microtubules contribute to slow axoplasmic transport, the movement of materials within long nerve fibers.

Dynamic Behavior:

Microtubules are not static. They constantly undergo:
- Growth (polymerization): Addition of tubulin dimers at the positively charged end (+).
- Shrinkage (depolymerization): Rapid disassembly of tubulin dimers, especially at the negatively charged end (-).
This dynamic instability allows microtubules to rapidly adapt to the cell’s needs.

Motor Proteins:

Molecular motors are proteins that “walk” along microtubule tracks, transporting cellular cargo.
Two main types of motor proteins interact with microtubules:
- Dynein: Moves cargo towards the negatively charged end (-) of the microtubule (retrograde transport). This is used by some viruses to travel within neurons.
- Kinesin: Moves cargo towards the positively charged end (+) of the microtubule (anterograde transport).

Microtubule-Targeting Drugs:

Several drugs target microtubule function for various purposes:
- Antiparasitic drugs: Mebendazole disrupts microtubules in parasitic worms.
- Antifungal drugs: Griseofulvin targets fungal microtubules.
- Antigout drug: Colchicine disrupts microtubule assembly, used to treat gout.
- Anticancer drugs:
  - Vincristine and vinblastine interfere with cell division by disrupting microtubules.
  - Paclitaxel stabilizes microtubules, inhibiting cancer cell growth.

Microtubule Polarity:

Microtubules have a defined polarity:
- Negative End (-): Located near the nucleus.
- Positive End (+): Points towards the cell periphery.
This polarity is important for motor protein directionality and overall cellular organization.

Mnemonic:

REaDY? AttacK! – This mnemonic can help remember the relationship between microtubule ends and motor proteins:
- REaDY – Negative end (-)
- AttacK – positive end (+)

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U01.01.026 Microtubule

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