3/24/26 Intermediate Filaments and Lamins

Definition of Lamin
- Type of intermediate filament protein beneath the nuclear envelope.
- Functions as a dense meshwork structure providing support to the nucleus.
Analogy of the Cell Structure
- Nucleus compared to a room with a nuclear envelope as the ceiling.
- Lamin filaments form a dense structure just below the nuclear envelope.
Growth Cone
- Introduction of the term 'growth cone' - structure that extends projections from a cell.
- Protrusion driven by coordinated cell biology and cell motility.
- Actin filaments play a role in forming the structure of the presynaptic side of a synapse.

Goals for the Week
- Complete discussion on intermediate filament proteins.
- Begin discussion on actin and myosin structures and their cellular functions.

Importance of Intermediate Filaments
- Used by pathologists to assess cancer staging by identifying the presence of lamin proteins in tumors.
- Various pathologies linked to intermediate filaments, including laminopathies.
Laminopathies
- Define as diseases associated with mutations in lamin proteins.
- Examples of lamin A-based pathologies:
- Dilated cardiomyopathy
- Skeletal muscle disorders
- Severe premature aging (Progeria)
Progeria
- Characterized by small stature and wrinkled skin indicative of very old age appearance despite young age.
- Result of point mutations in one allele of lamin A, such as single nucleotide substitution, significantly impacting health.

Cellular Studies Summary
- Nuclear morphology analyzed with various point mutations from Progeria patients.
- Dramatic changes observed in mutant nuclei compared to healthy nuclei (wild type).
- Nuclear integrity studies reveal extensive research linking mutations to disease states.

Actin Filament Overview
- Thin filaments approximately 8 nanometers in diameter.
- Localized contrasts drawn with microtubule behavior and structure, such as GTP caps in tubules as opposed to ATP interactions in actin.
- Actin monomers (G-actin) polymerize into filamentous actin (F-actin).
Polarization of Actin Filaments
- Distinction between plus (barbed) and minus (pointed) ends with differing growth rates.
- Plus end generally grows faster than the minus end due to lower critical concentration requirements.
Growth Mechanisms
- Actin has dynamic assembly and disassembly properties influenced by concentration gradients.
- Critical concentration for actin filament growth, with the plus end favoring growth due to a tenfold lower concentration threshold.
- Rate dynamics explained through critical concentration and equilibrium.

Treadmilling Concept Explained
- Defined as the dynamic process where polymerization at the plus end is balanced by depolymerization at the minus end, maintaining filament length.
- Significant in cellular processes, allowing cellular structures to move and change shape.
Experimentation with Actin Dynamics
- Visualization of treadmilling through microscopy techniques.
- Examples provided of cellular movements and actin organization.

Myosin Overview
- Myosins serve as molecular motors that travel along actin filaments.
- Myosin II identified as a significant player in muscle contraction and non-muscle activities like cytokinesis (cell division).
Myosin Movement Mechanism
- Described as having ATPase activity for energy conversion to mechanical movement.
- Two-headed myosin structure allowing it to walk along actin filament through conformational changes.
Myosin in General Cellular Function
- In addition to muscle contraction, myosins assist in intracellular transport, such as moving organelles along actin filaments.
- Example of Myosin V in cargo transport and its significance to cell functionality.

Actin Associated Proteins
- Various proteins interact with actin monomers and filaments to regulate actions such as assembly, organization, and dynamics.