unit 3 week 2 pt 3 Flashcards
What cytoskeletal element is primarily responsible for cellular motility?
Actin filaments, often working with myosin motors and actin-binding proteins.
What are some dynamic activities in non-muscle cells that rely on actin filaments?
Cytokinesis, phagocytosis, cytoplasmic streaming, vesicle trafficking, blood platelet activation, lateral movement of membrane proteins, cell-substratum interactions, cell locomotion, axonal outgrowth, and changes in cell shape.
Why is cell locomotion important in higher vertebrates?
It is required for tissue and organ development, blood vessel formation, axon development, wound healing, immune responses, and the spread of cancer.
What are the limitations of traditional cell locomotion research?
Most studies use cells moving over a flat 2D substrate, which may not fully represent how cells move in the body, where they traverse more complex 3D extracellular matrices.
How is cell locomotion similar to walking?
Like walking, cell movement involves repetitive steps: extending forward, forming temporary adhesion, generating traction, and retracting the trailing edge.
What are the four main steps of cell locomotion?
- Protrusion – A part of the cell surface extends in the direction of movement.
- Adhesion – The lower surface of the protrusion attaches to the substrate, forming temporary anchor points.
- Translocation – The bulk of the cell moves forward over these adhesion sites.
- Retraction – The cell releases its rear contacts, pulling the trailing edge forward.
What happens when a small piece of living tissue is placed in a culture dish?
Individual cells, typically fibroblasts, migrate out of the tissue onto the dish surface.
What are fibroblasts, and where are they commonly found?
Fibroblasts are the predominant cells in connective tissue.
How do fibroblasts move?
They flatten against the substrate, becoming fan-shaped with a broad front and a narrow tail. Their movement is erratic, sometimes advancing and sometimes retracting.
What is a lamellipodium, and what role does it play in fibroblast movement?
A lamellipodium is a broad, flattened, veil-like protrusion at the leading edge of the fibroblast. It provides temporary anchor points for cell movement.
What is unique about the structure of a lamellipodium?
It lacks cytoplasmic vesicles and other particulate structures, and its outer edge often exhibits an undulating, ruffled motion.
How does actin polymerization contribute to cell motility?
Actin monomers polymerize to generate force, propelling structures like lamellipodia forward, even without molecular motors.
What bacterial protein demonstrates actin-based motility, and how?
Listeria bacterium uses the ActA protein to activate actin polymerization, propelling it through the cytoplasm.
What human protein family functions similarly to ActA in mammalian cells?
The WASP/WAVE family activates the Arp2/3 complex, promoting actin polymerization at the leading edge of moving cells.
How do white blood cells move toward infection sites?
- They receive a chemical signal from the direction of infection.
- This triggers localized actin polymerization, polarizing the cell.
- The cell moves toward the stimulus, using actin-driven protrusions.
What disease results from a mutation in the WASP gene, and how does it affect immunity?
Wiskott–Aldrich syndrome – patients lack functional WASP protein, preventing their white blood cells from responding to chemotactic signals, leading to immune system deficiencies.
What initiates lamellipodium formation?
A stimulus at one end of the cell activates WASP proteins, which in turn activate the Arp2/3 complex (Step 1 & 2).
How does the Arp2/3 complex contribute to actin branching?
- Arp2/3 binds to an existing actin filament and mimics the barbed end (Step 3).
- ATP-actin monomers bind to the Arp2/3 template, forming a branched filament.
- Profilin promotes polymerization at barbed ends, extending filaments forward (Step 4 & 5).
- New Arp2/3 complexes attach to growing filaments, creating additional branches (Step 5).
- Capping proteins prevent further elongation of older filaments (Step 5).
- Cofilin binds to actin-ADP subunits, promoting disassembly at pointed ends (Step 6).
How is actin recycled?
Actin-ADP subunits released from disassembling filaments are converted back into ATP-actin by profilin, allowing continuous filament growth at the leading edge.
What does electron microscopy reveal about lamellipodia?
A branched, cross-linked actin network forms beneath the plasma membrane, with Arp2/3 complexes residing at Y-shaped junctions where new filaments branch from preexisting ones.
How does the actin network undergo treadmilling?
- Actin polymerization and branching occur at the front of the lamellipodium.
- Assembled filaments flow rearward and depolymerize at the back.
- Actin subunits are continuously recycled, allowing sustained protrusion.
How does the cell body follow the leading edge?
After lamellipodium protrusion, the bulk of the cell moves forward using traction forces at adhesion sites.
What are traction forces, and how are they studied?
They are generated at adhesion sites, where the cell grips the substrate. When cells migrate on an elastic material, their movements cause substrate deformation, which can be analyzed to calculate traction force distribution.
Where are the strongest traction forces in a migrating fibroblast?
Just behind the leading edge, where the cell adheres strongly to the substratum.
What is vinculin, and how does it help visualize adhesion sites?
Vinculin is a major focal adhesion protein. Fluorescently labeled vinculin reveals adhesion points where the migrating cell contacts the substrate.
How do adhesion sites change during migration?
- Focal complexes form at the leading edge.
- They either disassemble as the cell moves or mature into larger focal adhesions.
- Tension on adhesion sites promotes maturation into stronger, contractile adhesions.
What role do integrins play in adhesion?
Integrins are transmembrane proteins that connect the actin cytoskeleton to the extracellular matrix, transmitting traction forces for movement.
What triggers the formation of a lamellipodium?
A stimulus at one end of the cell activates Arp2/3 protein complexes via WASP proteins on the membrane surface.
How does the Arp2/3 complex contribute to actin filament formation?
Activated Arp2/3 binds to existing actin filaments, mimicking a barbed end, which allows ATP-actin monomers to attach and form new branched filaments.
What role does profilin play in actin polymerization?
Profilin promotes the addition of ATP-actin monomers to the free barbed ends of growing actin filaments.
How does actin branching continue?
New Arp2/3 complexes bind to the sides of recently formed filaments, nucleating additional branches.
What prevents uncontrolled filament growth?
Capping proteins bind to the barbed ends of older filaments, blocking further polymerization.
How does the lamellipodium move forward?
New filaments push the membrane outward, while older capped filaments undergo disassembly from their pointed ends.
What is the role of cofilin in actin dynamics?
Cofilin binds to actin-ADP subunits, promoting disassembly of older filaments.
What is actin treadmilling, and how does it contribute to cell movement?
Actin subunits are added to barbed ends at the front and lost from pointed ends at the rear, causing continuous renewal and movement of the actin network.
What are traction forces in cell locomotion?
Forces generated at adhesion sites pull the cell body forward by gripping the substrate.
What is the function of vinculin in cell movement?
Vinculin is found in focal adhesions and focal complexes, which help anchor the leading edge to the substrate.
How do focal complexes change during movement?
They either disassemble or mature into larger, more contractile focal adhesions.
How do actin and myosin contribute to cell movement?
Actin polymerization pushes the leading edge forward, while myosin II pulls the rest of the cell along.
What are keratocytes, and why are they useful for studying locomotion?
Keratocytes are fish epidermal cells with a broad, thin lamellipodium, making them ideal for studying actin-myosin interactions in movement.
Where is actin concentrated in a moving keratocyte?
Actin fills the advancing edge of the lamellipodium.
Where is myosin II located in a moving keratocyte?
Myosin II is concentrated in a band at the rear of the lamellipodium, generating contractile forces.
How does myosin II contribute to movement?
Myosin II forms small bipolar filaments that bind to the actin network and pull the cell body forward.
What other myosins contribute to cell movement?
Myosin I and other unconventional myosins assist in force generation in some organisms.
What classic experiment demonstrated axonal outgrowth?
In 1907, Ross Harrison cultured frog embryonic nerve tissue and observed axons growing outward, proving active elongation.
What structures are found at the tip of a growing axon?
The growth cone contains a lamellipodium, microspikes, and filopodia, all filled with actin filaments.
How do actin and microtubules contribute to axonal growth?
Actin filaments drive motile activity at the growth cone, while microtubules provide structural support and directionality.
What is the role of dynamic microtubules in the growth cone?
They extend into the actin-rich periphery, playing a role in steering the axon.
What is the growth cone, and what is its function?
The growth cone is a highly motile region at the tip of a growing axon that explores its environment and directs axonal elongation.
How do axons in the developing embryo navigate to their targets?
Axons follow defined paths by responding to physical features of the substratum and chemical signals in their environment.
What structures in the growth cone respond to environmental cues?
The lamellipodia and filopodia detect physical and chemical stimuli, guiding the axon toward attractive signals and away from repulsive ones.
What is netrin, and how does it influence axon growth?
Netrin is a diffusible protein that acts as an attractant, guiding axons toward their targets in the early embryo.
What is ephrin, and how does it function in axon guidance?
Ephrin is a nondiffusible membrane protein that binds to ephrin receptors on the growth cone, influencing axon navigation.
How do filopodia contribute to axon guidance?
Filopodia extend from the growth cone and serve a sensory function, detecting and responding to guidance cues like ephrin.
Why is the growth cone’s ability to make steering decisions crucial?
Proper nervous system wiring depends on the ability of growth cones to navigate correctly and reach their target organs.
How do different organs acquire their characteristic shapes?
Organs develop their structure through programmed changes in cell shape, which are largely controlled by the cytoskeleton.
What is the neural plate, and how does it form?
The neural plate is a tall epithelial layer formed by ectodermal cells along the dorsal surface of the embryo during gastrulation.
What cytoskeletal changes occur during neural plate formation?
Microtubules align parallel to the long axis of cells, causing them to elongate.
How does the neural plate bend to form the neural tube?
Actin microfilaments contract at one end of the cells, making them wedge-shaped and causing the entire layer to curve inward.
What is the significance of the neural tube?
The neural tube eventually develops into the entire nervous system of the animal.
