Unit 06 Pt5

Unit Overview

  • Unit 06: The Cytoskeleton in BIOL 331 – Advanced Cell Biology

  • Text Ref: MBoC (7th Ed): Chapter 16, Pages 1016 - 1018

Key Topics by Authors

  • Authors:

    • Hubert, Robert. Gould's Pathophysiology for the Health Professions, 6th Edition. Elsevier (HS-US), 2017

    • Banasik, Jacquelyn. Pathophysiology, 6th Edition. Elsevier (HS-US), 2018

  • Outline of Topics:

    • Cell Polarity Governed by Small GTPases in Budding Yeast

    • PAR Proteins and Anterior–Posterior Polarity in Embryos

    • Conserved Complexes Polarize Epithelial Cells and Control Growth

    • Dynamic Cell Polarity in Cell Migration

    • External Signals Directing Cell Migration Direction

    • Cytoskeletal Communication Supporting Cell Polarity and Locomotion

The Crawling Cell

  • Types of Cells That Move by Crawling:

    • Examples: Amoebae, bacteria, yeast, neural crest cells in development, germ cell migration in Drosophila, adult migratory cells (neutrophils, macrophages, osteoclasts, fibroblasts), and cancer cells (metastasis).

Mechanism of Cell Crawling

  • Crawling Process:

    1. Protrusion: Actin-rich structures extend forward.

    2. Attachment: The actin cytoskeleton connects to the substratum.

    3. Traction: The cytoplasm is drawn forward.

  • Characteristics: Depending on cell types, movements can be smooth (e.g., fish keratocytes) or jerky.

Protrusions of the Leading Edge

  • Types of Protrusions:

    • Filopodia: Long, thin, 1-D structures (e.g., growth cones of neurons).

    • Lamellipodia: Wide sheets, 2-D structures filled with a cross-linked actin mesh (e.g., seen in epithelial cells and fibroblasts).

    • Invadopodia (Podosomes): Larger projections, 3-D forms crucial for tissue barrier crossing (metastasis).

    • Bleb: Formed when the plasma membrane detaches from the cortex.

Case Study: Keratocytes

  • Description::

    • Epithelial cells from frog or fish epidermis, specialized for rapid movement (~30 μm/min).

    • Characterized by large lamellipodial extensions and small trailing cell bodies.

    • Notably used in wound healing; allows for observation of movement over time.

Lamellipodia Dynamics

  • Characteristics:

    • Actin networks are stationary regarding the substrate; exhibits treadmilling where plus ends point towards migration direction.

    • Branching of actin is facilitated by ARP complexes, creating a characteristic 70° angle.

Maintaining Unidirectional Movement

  • Requirements for Movement:

    • Interacting proteins for filament nucleation at leading edge must coordinate with depolymerization behind.

    • Cofilin preferentially binds to D-form actin, promoting treadmilling essential for directional movement.

Actin-Associated Proteins

  • Functional Role:

    • Focal adhesions connect migrating cells to the extracellular matrix.

    • Sarcomere-like contractions of myosin orient actin filaments to facilitate forward motion, ensuring engagement of integrins.

Regulation of Actin Rearrangement in Migration

  • Importance of Coordination:

    • Cell migration necessitates synchrony between protrusion and retraction.

    • Rho protein family (Cdc42, Rac, Rho) regulates actin dynamics and polarization.

Rho Proteins Overview

  • Functionality:

    • Small monomeric GTPases act as molecular switches in signaling pathways.

    • Activated Cdc42 induces filopodia, Rac drives lamellipodia, and Rho promotes stress fibers and focal contact formation.

Cdc42 Activation and Actin Polymerization

  • Mechanism:

    • Cdc42-GTP stabilizes WASp proteins to promote actin nucleation through the ARP 2/3 complex, enhancing cellular motility.

Other Examples of Cell Migration

  • Chemotaxis:

    • Cell movement in response to chemical gradients (e.g., neutrophils to bacterial infection, Dictyostelium towards cAMP).

Discussion Questions (Unit 06 – Part 5)

  • How does a cell crawl and what protrusions are involved?

  • Why are keratocytes an effective model for studying cell movement?

  • What roles do Rho family proteins play in cellular dynamics?

  • What factors stimulate cellular movement and how is this initiated?