Microtubule structure
Microtubules are composed of α- and β-tubulin heterodimers assembled into a hollow, tube like cylinder.
Dimers align end-to-end to form protofilaments, which then aggregate side by side (staggered packing) to create the microtubule’s wall.
Microtubule polarity
Microtubules have a (+) end (where β-tubulin is exposed) and a (-) end (associated with microtubule-organizing centers, MTOCs).
Provide several examples of the roles of microtubules within the cell.
Providing structure and support for the cell.
Creating highways for intracellular transport.
Separating chromosomes during cell division.
Allowing for cellular movement through cilia and flagella.
Role of MTOCs (Microtubule Organizing Centers)
MTOCs are structures that nucleate (start) and organize microtubules.
Centrosomes: The main MTOCs in animal cells, consisting of centrioles surrounded by pericentriolar material.
γ-tubulin Ring Complex (γ-TuRC): Essential for microtubule nucleation, binding αβ-tubulin dimers and acting as a template
Microtubule Dynamics
Dynamic Instability: Microtubules rapidly grow and shrink; their lifetime varies significantly across different cell types.
Critical Concentration (Cc): The minimum concentration of tubulin required for assembly; varies for (+) and (-) ends.
GTP cap model
GTP-bound β-tubulin stabilizes growing microtubules; hydrolysis to GDP exposes destabilizing regions that can lead to disassembly.
Rescue events can occur due to GTP-β-tubulin islands along the length of a microtubule, potentially pausing disassembly and allowing growth to resume.
Microtubule-Associated Proteins (MAPs)
Regulate stability and dynamics:
Stabilizing MAPs: MAP2, MAP4, Tau
Destabilizing MAPs: Kinesin-13, Op18/Stathmin
Growth Modulators: XMAP215 promotes growth, CLASP suppresses catastrophes.
Severing Proteins: Such as katanin, disassemble microtubules using ATP hydrolysis.
Medical Importance of Microtubule-Binding Drugs
Colchicine: Inhibits microtubule polymerization, used in treating gout by reducing inflammation.
Paclitaxel (Taxol): Stabilizes microtubules, preventing disassembly; used in cancer treatment (e.g., breast and ovarian cancer).