Lecture #62: Physiology: Cytoskeleton and Complex Cell Behavior I

What are the three main components of the cytoskeleton?

Microfilaments (actin), intermediate filaments, and microtubules.

What are the general functions of the cytoskeleton?

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

List the approximate diameters of the cytoskeletal elements.

Microfilaments: 6–8 nm; Intermediate filaments: 10 nm; Microtubules: 20–25 nm.

Which cytoskeletal element is the most stable?

Intermediate filaments.

What determines the type of intermediate filament expressed in a cell?

Tissue type and cell differentiation status.

List the major classes of intermediate filament proteins and their associated tissues.

Keratins – epithelial; Desmin – muscle; Neurofilaments – neurons; GFAP – glial; Vimentin – mesenchymal.

How are intermediate filaments used clinically?

As histopathologic markers to identify the tissue of origin of tumors.

Describe the basic structure of intermediate filaments.

Rod-shaped proteins with globular ends forming non-polar, energy-independent polymers.

What regulates intermediate filament assembly?

Phosphorylation by kinases affecting filament dynamics.

What is the function of intermediate filaments?

Provide mechanical strength, maintain cell shape, anchor organelles, and link cells via junctions.

What are desmosomes?

Cell–cell junctions connecting intermediate filaments of adjacent cells through cadherins (desmoglein, desmocollin).

What are hemidesmosomes?

Anchoring junctions linking intermediate filaments to the basal lamina via integrins and BP antigens.

Which junction type provides mechanical integrity between epithelial cells?

Desmosomes.

Which proteins connect intermediate filaments to hemidesmosomes?

Plectin, BP230, integrin α6β4, and BPAG2.

What autoimmune condition targets desmosomes?

Pemphigus vulgaris.

What autoimmune condition targets hemidesmosomes?

Bullous pemphigoid.

Compare pemphigus vulgaris and bullous pemphigoid by site of blister formation.

Pemphigus – suprabasal; Bullous pemphigoid – subepidermal.

Which intermediate filament mutation causes epidermolysis bullosa simplex?

Keratin 5 and 14 mutations causing fragile skin and blistering after birth.

Which intermediate filament disorder affects muscle?

Desminopathy – progressive skeletal, cardiac, and smooth muscle weakness.

Which nuclear filament disorder causes premature aging?

Progeria – due to lamin mutations.

Which neurodegenerative disorder is associated with neurofilament dysfunction?

Amyotrophic lateral sclerosis (ALS).

Which intermediate filament abnormality is found in astrocytomas?

Increased GFAP expression.

What is the role of microtubules?

Provide structural support, serve as tracks for vesicle transport, and form the mitotic spindle.

Describe microtubule structure.

Cylindrical polymers of α- and β-tubulin dimers arranged in 13 protofilaments.

What is the microtubule organizing center (MTOC)?

Centrosome; contains γ-tubulin ring complexes anchoring the minus ends of microtubules.

Which end of the microtubule elongates faster?

The plus (+) end, which is β-tubulin–exposed and GTP-rich.

What is dynamic instability?

Rapid switching between growth and shrinkage due to GTP cap hydrolysis on β-tubulin.

What are microtubule-associated proteins (MAPs)?

Regulate microtubule growth, stabilization, and interactions with other cytoskeletal elements.

What MAP is implicated in Alzheimer’s disease?

Tau protein – hyperphosphorylation causes neurofibrillary tangles and axonal degeneration.

What are centrioles?

Microtubule-based structures organizing the mitotic spindle and forming basal bodies of cilia.

Describe the “9+2” arrangement.

Nine outer microtubule doublets surrounding two central singlets in cilia/flagella.

What is the function of dynein?

Minus-end-directed motor protein responsible for retrograde transport and ciliary beating.

What is the function of kinesin?

Plus-end-directed motor protein responsible for anterograde transport of vesicles and organelles.

Which direction does dynein move along microtubules?

Toward the minus (–) end, typically toward the cell center.

Which direction does kinesin move along microtubules?

Toward the plus (+) end, typically toward the periphery.

What is the role of microtubule motors in neurons?

Enable anterograde and retrograde axonal transport of organelles and neurotransmitters.

Which viruses use dynein for retrograde transport in neurons?

Herpes simplex virus and rabies virus.

What are motile cilia?

Multiple, actively beating cilia found in respiratory epithelium and reproductive tracts.

What are primary cilia?

Single, immotile sensory cilia present on most cells (e.g., kidney, pancreas).

What are nodal cilia?

Cilia on embryonic nodal cells responsible for left-right body asymmetry.

What is intraflagellar transport (IFT)?

Process that moves proteins along the axoneme to and from the ciliary tip.

What are ciliopathies?

Genetic disorders caused by ciliary dysfunction affecting multiple organ systems.

What is Kartagener’s syndrome (Primary ciliary dyskinesia)?

Ciliary immotility causing chronic sinusitis, bronchiectasis, and situs inversus.

What is Bardet-Biedl syndrome?

Multisystem ciliopathy with obesity, polydactyly, renal cysts, hypogonadism, and retinal degeneration.

Which drugs disrupt microtubule dynamics in cancer therapy?

Vinblastine and taxol.

How does vinblastine affect microtubules?

Binds tubulin dimers, preventing spindle formation and blocking mitosis.

How does taxol (paclitaxel) affect microtubules?

Stabilizes microtubules, preventing depolymerization and blocking mitosis.

Which drug targets microtubules to treat gout?

Colchicine – binds free tubulin and inhibits neutrophil migration and degranulation.

What are the typical symptoms of gout?

Acute inflammatory arthritis, usually affecting the first metatarsophalangeal (big toe) joint.

Which microtubule-associated diseases involve transport defects?

Ciliopathies, Alzheimer’s disease, and certain viral infections.