cytoskeleton and microtubule lecture notes

Microtubules undergo dynamic changes within cells, particularly in terms of nucleation and polymerization.
- Nucleation can occur at various sites within the cell.
- Cells regulate the presence of proteins (divers) to ensure they exceed critical concentrations only in specific areas.
- Other proteins that promote depolymerization also play a role.

Observing individual microtubules (labeled A, B, and C), one can note:
- Microtubule A shows a pattern of growth followed by shrinkage over time.
- The plus ends of microtubules are continually growing and shrinking, moving to new locations.
- This dynamic behavior is crucial as microtubules act as tracks for intracellular transport.

Microtubule stability is critical for cellular function.
- Microtubules require good lateral cohesion; protofilaments maintain attachment along their length.
- GTP caps are formed at the ends of growing microtubules to stabilize them, as most subunits are in GDP form and show weak lateral cohesion.
Dynamic instability is a concept in which microtubules can rapidly grow and shrink, driven by GTP hydrolysis and protein interactions.

The study of microtubule dynamics has been enhanced by the discovery of drugs:
- Colchicine: A drug that causes depolymerization of microtubules.
- Taxol: Stabilizes microtubules to prevent depolymerization.
- Both drugs are significant in cancer therapy; they affect microtubule dynamics during mitosis, emphasizing their role in cell division.

Microtubule associated proteins (MAPs) help stabilize or destabilize microtubules.
- MAPs: General term for proteins that associate with microtubules, with varied functions.
- Specific examples include MAP2 and tau, which stabilize microtubules by coating them and preventing depolymerization.
- Cyclin-dependent kinases phosphorylate MAPs, influencing their function.

The structure of MAPs plays a significant role in microtubule stability:
- Large projection domains (like in MAP2) lead to loosely bundled microtubules with greater spacing, enabling the transport of larger cargo.
- Smaller projection domains (like in tau) result in tightly packed microtubules, limiting cargo size.

Certain MAPs, referred to as plus-end tracking proteins or +TIPs, influence polymerization at the microtubule plus end.
- They stabilize the ends and can facilitate transport toward this end, integrating with the overall dynamic instability of the microtubules.
- The relationship between MAPs and microtubule dynamics involves both stabilization and cargo transport functions.

Experiments, such as the radioactive amino acid injection in squid axons, show the dynamics of protein movement and microtubule interaction:
- Radioactive proteins synthesized in the cell body move down the axon, revealing differences in protein banding based on travel distance.
- Various classes of kinesin proteins (a type of motor protein) are identified, crucial for cargo transport along microtubules.

Kinesins are motor proteins defined by their structural components:
- All kinesins share similar structural features: a head domain, a neck, and a tail.
- Kinesin-1: The most abundant and is characterized as a conventional kinesin with two heavy chains and two light chains.
- Kinesin-2: Has a heterotrimeric composition, different heavy chains, and additional light chains, indicating diversity in cargo handling.
- The importance of head, neck, and tail structure underlies the various functions of kinesins in cellular transport.