Lecture #63: Physiology: Cytoskeleton and Complex Cell Behavior II

What are the three major components of the cytoskeleton?

Microfilaments (actin), intermediate filaments, and microtubules.

What are the major functions of the cytoskeleton?

Support, motility, proliferation, morphogenesis, and intracellular transport.

What are microfilaments composed of?

Actin polymers (F-actin) formed from globular G-actin monomers.

What is the polarity of actin filaments?

Barbed (+) end grows faster; pointed (–) end grows slower.

What is actin treadmilling?

Simultaneous polymerization at the barbed end and depolymerization at the pointed end maintaining steady-state turnover.

Which cellular processes depend on actin dynamics?

Cell migration, cytokinesis, phagocytosis, and membrane protrusions (filopodia, lamellipodia, microvilli).

What are the main actin-binding proteins that regulate nucleation?

WASp and Arp2/3 complex.

Which actin-binding proteins regulate polymerization?

Formins (unbranched growth) and VASP (prevents capping).

Which proteins sever actin filaments?

ADF/cofilin, fragmin, severin.

Which proteins cap actin filaments?

Gelsolin and tropomodulin.

Which actin-binding proteins cross-link or bundle actin?

α-actinin, filamin, spectrin, fimbrin, and villin.

What protein stabilizes actin in striated muscle?

Tropomyosin.

Which protein regulates actin-myosin interaction in smooth muscle?

Caldesmon.

What are the four main actin networks in non-muscle cells?

Stress fibers, contractile ring, cortical actin, and cell-migration pseudopods.

What is the role of actin in red blood cells?

Forms a spectrin–actin lattice maintaining biconcave shape and membrane stability.

What disease results from spectrin deficiency?

Hereditary spherocytosis causing fragile, spherical RBCs and hemolytic anemia.

How does malaria interact with the RBC cytoskeleton?

Plasmodium proteases modify spectrin–actin networks to facilitate invasion and exit.

What is the role of myosin motors?

ATP-dependent movement along actin filaments toward the barbed (+) end.

Which direction do myosins move actin filaments?

From the pointed (–) end toward the barbed (+) end.

What are unconventional myosins I and V responsible for?

Cargo transport of vesicles and organelles.

What regulates actin–myosin contraction in muscle?

Calcium binding to troponin C, causing tropomyosin to move off binding sites.

What are the components of the troponin complex?

Troponin C (binds Ca²⁺), Troponin I (inhibitory), and Troponin T (binds tropomyosin).

Which troponin isoforms are specific to cardiac muscle?

Troponin I and T — used clinically to detect myocardial injury.

What is Duchenne muscular dystrophy caused by?

X-linked mutation in dystrophin gene → loss of cytoskeletal–membrane stability in muscle.

What is dystrophin’s function?

Links cortical actin to the sarcolemma; part of the α-actinin superfamily.

How does dystrophin deficiency affect muscle?

Muscle fiber degeneration exceeding regenerative capacity → progressive weakness.

What autoimmune disorders target cytoskeletal junctions?

Pemphigus vulgaris (desmosomes) and bullous pemphigoid (hemidesmosomes).

What are adherens junctions and their role?

Cadherin-based cell–cell adhesions connecting to actin cytoskeleton; maintain epithelial integrity and transmit mechanical force.

How do adherens junctions differ from desmosomes?

Adherens connect to actin; desmosomes connect to intermediate filaments.

What are dense bodies in smooth muscle?

α-actinin-rich anchors for actin filaments analogous to Z-lines in striated muscle.

Which intermediate filaments associate with smooth muscle dense bodies?

Vimentin and desmin.

What coordinates contraction during cytokinesis?

Microtubules orient and signal actin-myosin contractile ring formation at the cleavage furrow.

Which protein links all three cytoskeletal systems?

Plectin — integrates actin, intermediate filaments, and microtubules.

What toxins disrupt actin filaments?

Cytochalasins (block barbed-end growth), botulinum C2 toxin (ADP-ribosylates actin), and phalloidin (stabilizes filaments).

How do pathogens exploit actin?

Listeria and Shigella use Arp2/3-mediated actin “comet tails” for intracellular movement.

What is Wiskott–Aldrich syndrome?

X-linked WASp mutation impairing actin nucleation in hematopoietic cells → immunodeficiency, eczema, thrombocytopenia.

What cytoskeletal defect underlies hereditary spherocytosis?

Spectrin mutation → weakened RBC membrane → hemolysis.

What clinical marker confirms myocardial infarction?

Elevated cardiac troponin I or T.

What is the functional significance of actin–microtubule coordination?

Essential for cell migration, polarity, and division.