2/11 Lecture

Cytoskeleton and Intermediate Filaments Study Notes

Focus of today's lecture: Cytoskeleton, specifically Intermediate Filaments.
Structure and function of Intermediate Filaments will be contrasted with Actin and Microtubule filaments.

Definition: Intermediate filaments are a key component of the cytoskeletal structure in eukaryotic cells.
Complexity: Intermediate filaments are generally considered less dynamic and complicated than Actin or Microtubules.
Structural Stability:
- Intermediate filaments are stable and maintain a consistent length.
- Lack motor proteins; serve more structural functions.

Structural Formation:
- Formed from long, twisted proteins resembling ropes.
- Provide structural reinforcement to the cell.
Comparison to Other Filaments:
- They are labeled as 'intermediate' as they fall between the thickness of Actin filaments and Microtubules.
- Not as thin as Actin ( $ext{Actin} < ext{Intermediate Filaments} < ext{Microtubules}$ ).

Monomer Structure:
- Comprised of long alpha-helical proteins with sticky ends at the C and N termini.
Dimer Formation:
- Monomers coil to form dimers (two monomers coiling together).
- The first assembly is parallel.
Tetramer Formation:
- Two dimers coil together in an antiparallel arrangement (C-terminus of one dimer aligns with N-terminus of another).
- Eight tetramers bundle together to form the intermediate filament ( $8 ext{ tetramers} = 32 ext{ monomers}$ ).

End Structure:
- Each bundle has ends that are offset; leading to 16 monomers protruding from each end.
Strength:
- Largely thanks to noncovalent interactions; create robust structures likened to ropes.
- Comparison: Like a thick rope made of many fibers rather than single strands.
Stability:
- They have no designated plus or minus end; appear identical on both ends.

Diversity in Cell Types:
- Unlike Actin or Microtubules which have uniform structures across cell types,
- Intermediate filaments include various homologous proteins depending on the cell type.
- Examples include Keratin in skin cells and Neurofilaments in neurons.
Common Types:
- Keratins, neurofilaments, desmin in muscle cells, and lamins in the nucleus (sometimes referred to as nucleoskeleton).
- Different cells may contain a mix of various intermediate filaments.

Cell Integrity:
- Intermediate filaments contribute significantly to the structural integrity of tissues.
- Forces connecting intermediate filaments between neighboring cells reinforce tissue cohesion.

Example of Keratin Mutation:
- Can lead to congenital defects such as blistering; severe mutations prevent proper skin formation.
Impact:
- Issues with intermediate filament integrity can lead to serious complications, frequently affecting survival.

Plectin:
- A crucial protein linking various cytoskeletal elements together (microtubules, intermediate filaments).
- Key in establishing structural coordination amongst cytoskeletal components.

Definition:
- Sits beneath the plasma membrane; provides structural support.
Components:
- Primarily made of spectrin, which interacts with short actin filaments and various transmembrane proteins (e.g. Glycophorin).

Function:
- Creates compartments in cells that are not fully separated by membranes; prevents diffusion of proteins across junctions.
Formation:
- Septins consist of 14 different proteins that can combine to form various structures.

Intermediate filaments play a critical role in the structural integrity of tissues through strong noncovalent interactions.
Mutations in these structural proteins can result in significant physiological issues.
Coordinative proteins like plectin and septins are essential for maintaining cytoskeletal organization and spatial separation within cellular environments.