76. Physiology | Cytoskeleton and Complex Cell Behavior I

Desmosomes

Auto‑antibodies against desmoglein cause pemphigus vulgaris (flaccid, suprabasal blisters).

Hemidesmosomes

BPAG1/BPAG2 disruption underlies bullous pemphigoid; biopsy shows linear IgG at the dermo‑epidermal junction

Zonula occludens (tight junctions)

Maintain paracellular barrier

Gap junctions

Connexin channels for electrical/chemical coupling

Adherens junctions

Cadherin/actin–based; involved in early cell–cell adhesion, not tense bullae

Cytokeratin

Marks epithelial cells

GFAP

Marks glial tumors

Desmin

Marks mm. origin, mutations give protein aggregates, cardiomyopathy, limb‑girdle weakness

Vimentin

Marks mesenchymal cells/sarcomas

Neurofilament

Marks neuronal tumors

Microtubule dynein arms within cilia

Loss of dynein ATPase halts ciliary beating, producing situs inversus, bronchiectasis, sinusitis, infertility

Kinesin motor proteins

lus‑end transport; defects cause other trafficking issues

Keratin filaments a/w

epithelial strength

G-actin polymerization

Affects cell motility/phagocytosis

Intermediate filaments in desmosomes a/w

Skin integrity

Dystrophin

Absence causes Duchenne/Becker muscular dystrophy (X‑linked, no IF aggregates).

Lamin A/C

Nuclear IFs; defects can cause progeria or cardiomyopathies with conduction blocks

Nestin

Developmental IF in neural stem/endothelial cells

A 45-year-old woman has progressive weakness of proximal muscles and a family history of both cardiac failure and skeletal muscle abnormalities. Muscle biopsy shows abnormal “intermediate filament–like” protein aggregates disrupting myofibrillar organization. A mutation in which protein is most likely responsible for her symptoms?

A. Dystrophin
B. Desmin
C. Lamin A/C
D. Vimentin
E. Nestin

B

• A. Dystrophin ❌ — Absence causes Duchenne/Becker muscular dystrophy (X‑linked, no IF aggregates).

• B. Desmin ✅ — IF in all muscle types; mutations give protein aggregates, cardiomyopathy, limb‑girdle weakness.

• C. Lamin A/C ❌ — Nuclear IFs; defects can cause progeria or cardiomyopathies with conduction blocks.

• D. Vimentin ❌ — Mesenchymal IF; not typically myopathic.

• E. Nestin ❌ — Developmental IF in neural stem/endothelial cells.

Paclitaxel

Stabilizes microtubules; anti‑mitotic chemo

Vinblastine

Binds β‑tubulin ends; anti‑mitotic chemodisrupts microtubule assembly and prevents mitosis.

Colchicine

Binds free dimers, prevents polymerization, curbs neutrophil chemotaxis/degranulation in gout.

Indomethacin

NSAID; blocks COX enzymes but no microtubule effect

Fluconazole

Antifungal azole