STEPTRACKERBIOCHEMISTRY + PATHOLOGY + PHARMACOLOGY | CELL BIOLOGY | HIGH-YIELD REVIEW

Cytoskeleton, Cilia & Motor Proteins

Three filament systems by size, the 9 + 2 cilium, and the motors that carry cargo — plus the drugs and stains that use them.

FOCUS ON

Microfilaments (actin, thinnest) = movement, microvilli, muscle. Intermediate filaments = structure; each tissue has its own type (vimentin, desmin, cytokeratin, GFAP, neurofilaments) → IHC tumor stains. Microtubules (α/β-tubulin, thickest) = cilia, spindle, axonal transport. Dynein walks toward the minus end (retrograde); kinesin toward the plus end (anterograde). Defective dynein arm → primary ciliary dyskinesia.

ELEMENT

STRUCTURE · ROLE

EXAMPLES · MARKERS

DRUG · DISEASE

Microfilaments

actin · ~7 nm

Polymerized actin; contraction, cytokinesis, microvilli, adherens junctions

Muscle sarcomeres, intestinal microvilli

Phalloidin and cytochalasins (research)

Intermediate filaments

~10 nm

Strong rope-like structural support; tissue-specific

Vimentin (mesenchyme) · desmin (muscle) · cytokeratin (epithelium) · GFAP (astrocytes) · neurofilaments (neurons) · lamins (nucleus)

Used to identify a tumor's tissue of origin

Microtubules

tubulin · ~25 nm

Hollow tubes of α/β-tubulin dimers, 13 protofilaments; grow from the centrosome (+ end out)

Mitotic spindle, cilia, flagella, axonal transport

Vincristine, vinblastine, colchicine (block polymerization) · paclitaxel (stabilizes)

Cilia & flagella

9 + 2 microtubule axoneme; basal body has 9 triplets; dynein arms slide doublets

Airway, fallopian tube, ependyma, sperm flagellum

Primary (nonmotile) cilia → polycystic kidney links

Dynein

ATPase motor moving toward the minus end (cell body) — retrograde

Ciliary beating, axonal return transport

Viruses travel retrograde: HSV, rabies, polio, tetanus toxin

Kinesin

ATPase motor moving toward the plus end (periphery) — anterograde

Carries vesicles down axons

—

Primary ciliary dyskinesia

Kartagener · AR

Absent/defective dynein arm → immotile cilia

Bronchiectasis, chronic sinusitis, recurrent otitis, infertility, situs inversus in ~50%

↓ nasal nitric oxide; sperm immotile but viable

Microtubule drugs

Block polymerization or depolymerization

Vinca alkaloids, taxanes, colchicine (neutrophils in gout), griseofulvin (fungi), mebendazole/albendazole (helminths)

Vincristine → neuropathy; vinblastine → marrow

Chédiak-Higashi syndrome

AR · LYST

Microtubule-dependent lysosomal trafficking defect → phagosome–lysosome fusion fails

Recurrent pyogenic infections, partial albinism, peripheral neuropathy, giant granules in neutrophils

Bleeding (platelet dense granules)

Cell junctions

Tight (zona occludens, claudins) · adherens (cadherins, actin) · desmosomes (desmoglein, keratin) · gap (connexons) · hemidesmosomes (integrins, BP antigens)

Epithelia

Pemphigus (desmosomes) · pemphigoid (hemidesmosomes) · loss of E-cadherin → metastasis

Picture it — filaments, cilia and motors

Three filament sizesActin (thinnest), intermediate filaments (rope-like), microtubules (hollow, 13 protofilaments).

Ciliary axonemeNine outer doublets around two central microtubules; dynein arms make the doublets slide.

Motor directionKinesin carries cargo toward the + end (out); dynein toward the − end (back to the cell body).

Schematic diagrams, not to scale.

Mechanism — axonal transport

Cell body (− end)

→

KinesinAnterograde

→

Synapse (+ end)

→

DyneinRetrograde

→

Cell bodyRabies, HSV, tetanus toxin ride here

Mnemonic: Kinesin goes K-out to the periphery; Dynein comes back Down to the cell body.

Intermediate filament stains

FILAMENT

TISSUE

TUMOR EXAMPLE

Cytokeratin

Epithelium

Carcinomas

Vimentin

Mesenchyme

Sarcomas

Desmin

Muscle

Rhabdomyosarcoma, leiomyosarcoma

GFAP

Glia

Astrocytoma, GBM

Neurofilament

Neurons

Neuroblastoma

How it's tested

COMMON CONFUSIONPaclitaxel stabilizes microtubules (can't disassemble the spindle); vinca alkaloids and colchicine prevent assembly. Both stop mitosis.

THE TRAPAn infertile man with chronic sinusitis and bronchiectasis may have normal sperm counts — the sperm just can't swim.

YOUR APPROACHSize of filament → protein → function → drug that targets it or the stain that shows it.

If you see… think…

Bronchiectasis, sinusitis, dextrocardia → Kartagener (dynein arm)

Rabies or HSV spreading to the CNS → retrograde transport (dynein)

Chemo drug causing peripheral neuropathy → vincristine

Microtubule stabilizer for breast/ovarian cancer → paclitaxel

Gout drug blocking neutrophil microtubules → colchicine

Tumor positive for GFAP → astrocytic glioma

Tumor positive for desmin → muscle origin

Giant granules in neutrophils + albinism → Chédiak-Higashi

9 + 2 arrangement → ciliary axoneme

Antibodies against desmosome proteins → pemphigus vulgaris