Lectures 23-24 NPB110A Cytoskeleton and Molecular Motors W25 Furlow

Lecture Overview

• NPB 110A: "Foundations: From Molecules to Individuals" Lecture 23: The Cytoskeleton (part I)

  • Dr. Furlow

Learning Objectives for Lecture 23

• Define the structure and location of the three major cytoskeletal elements.

• Explain the general role of cytoskeletal elements in cell polarity and intracellular trafficking.

• Explain the molecular basis of actin dynamics, including the role of ATP.

• Describe how specific drugs can alter actin filament dynamics.

Importance of the Cytoskeleton

• Cell Functionality:

  • Provides structural support and helps maintain cell shape.

  • Facilitates cell mobility (motility) and intracellular transport (e.g. nuclear transport, secretion).

  • Essential for cell division during mitosis and meiosis.

  • Involved in morphogenesis, which refers to the changing shape of cells.

  • Plays a role in cell signaling, especially in response to mechanical stress, activating signaling pathways.

• Health Implications:

  • Defects in cytoskeletal structures can lead to various diseases including:

    • Cancers

    • Neurological disorders

    • Skin disorders

Types of Proteins in the Cytoskeleton

• Microfilaments (Filamentous Actin)

  • Interacts with myosins (molecular motors).

  • Involved in muscle contraction and structural support to cilia and flagella.

  • Moderately flexible.

• Microtubules

  • Structural support for the nuclear membrane and organelles.

  • Form the mitotic spindle and tracks for kinesins (motor proteins that move towards the + end) and dyneins (motor proteins that move towards the - end).

  • Least flexible of the three types.

• Intermediate Filaments

  • Provide structural support in various tissues (e.g., skin, hair, nails).

  • Most flexible type of cytoskeletal protein.

Cytoskeletal Networks Within Cells

• Microtubule Organization:

  • Microtubules and microfilaments are critical for cellular organization and structure.

  • Maps of cultured cells highlight the arrangement of cytoskeletal components in interphase and mitotic cells.

Cell Polarity

• Dependent on a well-structured cytoskeleton.

  • Different cell types exhibit unique organizing principles for their cytoskeletal elements.

• Epithelial Cells:

  • Show preferential localization of cytoskeletal elements at distinct cellular regions.

  • Adherens junctions, desmosomes, and hemidesmosomes play a role in cell adhesion and structural integrity.

Actin Dynamics

• Structure of Actin Filaments:

  • Each microfilament has + and – ends; actin monomers are predominantly added at the + end, though slow addition can occur at the – end.

  • Actin filaments can be altered by drugs such as cytochalasin B.

• Polymerization Process:

  • G-Actin (globular actin) can bind ATP, which is hydrolyzed to ADP during polymerization.

  • Treadmilling occurs when there’s a net addition of monomers at the + end and net loss at the – end. This is critical for dynamic cellular processes.

Pharmacological Regulators of Cytoskeletal Dynamics

• Drugs that affect actin dynamics can also be used in cancer treatment due to their impact on cellular movement and structure.

Molecular Motors and Microtubules

• Motor proteins play critical roles in cellular transport and are powered by ATP hydrolysis.

  • Types of Motor Proteins:

    • Myosin: Generally moves along actin filaments towards the + end.

    • Kinesin: Transports cargo towards the + end of microtubules.

    • Dynein: Transports cargo toward the - end, typically towards the nucleus.

Intermediate Filaments

• Formed from proteins like keratin, which can lead to disorders such as epidermolysis bullosa simplex.

• Progeria:

  • Caused by a mutation in the LMNA gene affecting the integrity of nuclear structures, leading to accelerated aging.

  • Life expectancy is notably reduced, highlighting the importance of intermediate filaments in developmental biology.