Chapter 14: Cellular Movement: Motility & Contractility

Chapter 14: Cellular Movement: Motility & Contractility

1. Microtubule Associated Motor Proteins

  • Definition: Microtubule associated motor proteins, also known as mechanoenzymes, are proteins that facilitate the movement of cargo along cytoskeletal tracks within the cell.

2. Cytoskeleton for Transport

  • Microfilaments (Actin):

    • Characteristic: Thin and flexible.

    • Function: Suitable for small-scale transport within the cell.

  • Microtubules:

    • Characteristic: Rigid and polar.

    • Function: Ideal for long-distance transport of vesicles and organelles.

    • Polarization: Microtubules possess directional polarity, enabling motor proteins to move toward either the plus end or the minus end.

3. Kinesin Motor Protein

  • Definition: Kinesin is a microtubule motor protein that moves typically towards the plus (+) end of the microtubule, which is away from the cell center and towards the plasma membrane.

  • Structure of Kinesin:

    • Consists of:

    • Two intertwined heavy chains.

    • Two globular “heads” located at one end.

    • A tail region at the other end that binds to cargo.

  • Functionality:

    • The globular heads:

    • Bind to β-tubulin.

    • Hydrolyze ATP to fuel movement along the microtubules.

Steps of Kinesin Movement

  1. One “foot” (globular head) binds to the microtubule, becoming the “front head.”

  2. ATP binds to the front head, this energy facilitates the swinging of the rear head forward to the next binding site.

  3. ATP is then hydrolyzed into ADP and inorganic phosphate (Pi), releasing energy that causes the new rear head to detach.

  4. This cycle repeats as the rear head swings forward again upon ATP binding.

4. Dynein Motor Protein

  • Definition: Dynein is a larger and more complex motor protein that moves towards the minus (-) end of microtubules, thus transporting cargo toward the cell center.

  • Binding Mechanism:

    • Cannot bind directly to cargo. Instead, it connects via:

    • Dynein → Dynactin complex → Spectrin & Ankyrin adaptor proteins → Cargo.

5. Cilia & Flagella

  • Structure:

    • Both cilia and flagella contain a core of microtubules arranged in a structure known as the "axoneme."

    • The axoneme consists of:

    • 9 outer microtubule doublets.

    • 2 central microtubules.

  • Movement Generation:

    • Dynein motor protein arms and radial spokes contribute to the movement through the bending structure rather than sliding completely.

    • The structure bends due to nexin links and radial spokes redirecting the force generated by dynein.

Differences in Motion

  • Cilia:

    • Short.

    • Multiple per cell (hundreds).

    • Back-and-forth beating motion for moving fluids across the cell surface or propelling the cell.

  • Flagella:

    • Long.

    • Few per cell (usually one or a few).

    • Whip-like or undulating motion, primarily for propulsion through fluid.

6. Myosins

  • Definition: Myosins are a family of motor proteins that interact with microfilaments, specifically actin filaments, to facilitate movement within cells.

  • Basic Structure:

    • Comprised of a heavy chain with a globular head domain and often a tail domain that binds to cargo or helps form filaments.

Myosin Functions

  • Major Types of Myosins in Humans:

    • Myosin I:

    • Function: Vesicle transport across actin filaments in non-muscle cells.

    • Myosin II:

    • Function: Muscle contraction through the formation of thick filaments in skeletal, cardiac, and smooth muscles.

    • Works with actin to shorten sarcomeres.

    • Myosin V:

    • Function: Organelle and vesicle transport, including mitochondria and pigment granules.

    • Myosin VI:

    • Unique characteristic: Moves towards the minus (-) end of actin which is atypical for myosins.

    • Function: Involvement in endocytosis.

    • Myosins III, IV, and VII-XIX:

    • Special functions including involvement in:

      • Stereocilia in the inner ear.

      • Cell migration.

      • Additional specialized functions.

7. Related Disorders

  • Griscelli’s Disease:

    • Definition: Rare genetic disorder that affects melanosome transport within melanocytes due to a mutation in Myosin V.

    • Effects:

    • Impaired transport of pigments leads to silvery hair.

    • Impaired secretory vesicle function in T cells resulting in immune dysfunction.

    • Disrupted vesicle and organelle transport in brain cells causing neurological issues.

  • Situs Inversum Viscerum:

    • Definition: A condition where the organs are flipped left-to-right due to defective motile cilia in the “embryonic node.”

    • Effects: Cilia fail to generate proper leftward flow, disrupting the body's axis determination.

  • Usher’s Syndrome:

    • Definition: Rare inherited disorder involving defective nonmotile cilia in sensory cells (e.g., stereocilia in inner ear).

    • Effects: Causes both hearing loss and progressive vision loss.

8. Muscle Fiber Arrangement & Contraction

  • Skeletal Muscle Fiber Structure:

    • Composed of muscle fibers known as myofibrils which are surrounded by specialized endoplasmic reticulum known as the sarcoplasmic reticulum (SR) that stores Calcium ions.

    • T-tubules connect the cell membrane with the SR and assist in transmitting electrical signals into the cell.

Mechanism of Muscle Contraction

  • Sliding Filament Theory:

    • Definition: Muscle contraction occurs when thin filaments (actin) slide past thick filaments (myosin), resulting in the shortening of the sarcomere, the smallest contractile unit of a muscle fiber.

  • Components Involved in Structure and Stability:

    • Z Lines (Z Discs):

    • Dark zig-zag lines that delineate the ends of each sarcomere, anchoring the (+) ends of actin filaments.

    • During contraction, Z lines move closer together.

    • CapZ:

    • A capping protein at the (+) end of actin filaments which maintains filament length by preventing actin from growing or shrinking.

    • Nebulin:

    • A long protein that stabilizes and determines the length of actin filaments, functioning like a “molecular measuring tape.”

    • M Line:

    • Located in the center of the sarcomere; anchors thick myosin filaments and contains stability proteins like myomesin and M-protein.

Process of Muscle Contraction

  1. Neurotransmitter Release: Motor neuron axon terminals release acetylcholine (ACh) across the neuromuscular junction.

  2. ACh Binding: ACh binds to receptors on the motor end plate of the muscle fiber.

  3. Depolarization: This binding opens sodium (Na+) channels, allowing sodium to enter, thus depolarizing the muscle membrane.

  4. Action Potential: The electrical change initiates an action potential, which propagates across the sarcolemma and down into the T-tubules.

  5. Calcium Release: Voltage change in T-tubules triggers calcium (Ca2+) channels in the SR to open and release Ca2+ into the cytoplasm.

  6. Troponin Activation: Ca2+ binds to troponin, causing a structural change that exposes myosin binding sites on actin filaments.

  7. Cross-Bridge Formation: Myosin heads hydrolyze ATP, allowing them to bind and form cross-bridges with actin.

  8. Power Stroke: Myosin heads pivot and pull actin toward the M line, completing the contraction cycle.

  9. Detachment: ADP is released, and a new ATP binds to the myosin head, leading to detachment of myosin from actin.

  10. Repeating Cycle: The process repeats as long as Ca2+ is present in sufficient quantities.

Contraction Results

  • The sliding of filaments shortens the sarcomere resulting in muscle contraction.

  • When the nerve signal ceases, calcium is reabsorbed, leading to muscle relaxation.