Oct 14 220

This lecture is a continuation covering Chapter 17, focusing on microtubules and their functions.
There was a technical issue with recording previous lectures, causing some concern among students.

Fluorescent labeling allows for visualization of proteins, such as tubulin, using specialized microscopy techniques known as fluorescence microscopy.
Tubulin is a principal component of microtubules.

Cell Shape Determination: Microtubules determine the shape of the cells by organizing themselves in specific locations and adopting filamentous forms.
Tracks for Motor Proteins: Microtubules serve as tracks for motor proteins to transport cellular cargo, facilitating movement from one part of the cell to another.
Cell Division: Microtubules are crucial during cell division (mitosis) as they form mitotic spindles that segregate chromosomes into daughter cells.

Microtubules are hollow and tubular structures, consisting primarily of tubulin heterodimers (composed of alpha and beta tubulin).
They typically consist of 13 protofilaments, which stagger in an alpha-beta pattern for stability.
Nucleation and Assembly: Microtubules grow from nucleation sites called microtubule organizing centers, specifically emanating from centrosomes.
Microtubules have distinct structural ends:
- Plus end: Site of assembly.
- Minus end: Located at the centrosome, site of nucleation.
Microtubules are dynamic, capable of rapid assembly and disassembly, which is regulated by the availability of GTP-bound tubulin dimers.

Centrosomes are essential microtubule organizing centers, typically containing two centrioles positioned perpendicular to each other.
Centrioles play a role in cell division but are not directly involved in nucleation; they provide a matrix for the attachment of gamma tubulin, which forms nucleation templates.
Gamma Tubulin: A type of tubulin that forms rings crucial for initiating microtubule assembly.

Microtubules display dynamic instability, transitioning between phases of rapid growth and rapid shrinkage due to GTP hydrolysis rates compared to dimer addition rates.
The presence of a GTP cap stabilizes microtubules and promotes assembly, while GDP-bound dimers favor disassembly due to conformational changes.
This dynamic nature allows cells to adapt their cytoskeleton to changing needs, such as during cellular migration or division.

The assembly of microtubules is facilitated through:
1. GTP-Bound Dimers: When ample GTP-bound dimers are available, they add to the plus end, promoting rapid growth.
2. Hydrolysis Effects: As GTP is hydrolyzed to GDP, the microtubules can destabilize and undergo disassembly if the GTP cap is lost.

MAPs play various roles in stabilizing microtubules, enhancing assembly, and regulating interactions with other proteins. Examples include:
- Tau: Stabilizes microtubule structure, with implications in neurodegenerative diseases like Alzheimer’s due to its phosphorylation state.
- EB Proteins: Facilitate the binding of tubulin dimers to microtubules, enhancing stability and assembly.

Motor proteins such as kinesins and dyneins transport cellular materials along microtubules:
- Kinesins: Move cargo towards the plus end of microtubules (outwardly).
- Dyneins: Move cargo towards the minus end (inwardly), providing a mechanism for bidirectional transport in cells.
Both motor proteins operate using ATP hydrolysis, converting chemical energy into mechanical work for movement along microtubules.

Cilia and flagella are extensions of cells that contain a specific arrangement of microtubules, typically termed the axoneme, which consists of 9 doublet microtubules surrounding a central pair.
Basal Bodies: These act as microtubule organizing centers for cilia and flagella and are structurally similar to centrioles, facilitating their formation and stability.
The bending movements of cilia are controlled by dynein activity, facilitating effective sweeping motions for mucous clearance, especially in the airway epithelium.