Cytoskeleton Organization, Behavior, and Cytoskeletal Defects

Vocabulary flashcards covering actin and microtubule accessory proteins, motor proteins, and cytoskeletal defects including Hereditary Spherocytosis and Muscular Dystrophies.

Formin

An actin accessory protein that nucleates actin assembly and remains associated with the growing plus end of the filament.

Arp2/3 Complex

An actin accessory protein complex that nucleates actin assembly to form a branched web and remains associated with the minus end.

Thymosin

An actin accessory protein that binds actin monomer subunits and prevents their assembly into filaments.

Profilin

An actin accessory protein that binds actin monomer subunits and speeds filament elongation.

Tropomodulin

An actin accessory protein that prevents assembly and disassembly at the minus end of an actin filament.

Cofilin

An actin accessory protein that binds ADP-actin filaments and accelerates their disassembly.

Gelsolin

An actin accessory protein that severs actin filaments and binds to the newly created plus end.

Tropomyosin

An actin accessory protein that binds along the side of an actin filament to stabilize it.

Stathmin

A microtubule accessory protein that binds tubulin heterodimers/subunits and prevents microtubule assembly.

+TIPs

Plus-end tracking proteins that remain associated with growing plus ends of microtubules and can link them to cellular structures such as membranes.

$$\gamma\text{-TuRC}$$

The $\gamma$-tubulin ring complex that nucleates microtubule assembly and remains associated with the minus end.

Microtubule-Organizing Center (MTOC)

A specific cellular location from which microtubules are nucleated and grow outward toward their plus ends; in animal cells, the principal MTOC is the centrosome.

Centrosome

The major MTOC in animal cells, located adjacent to the nucleus, consisting of a pair of centrioles embedded in a fibrous matrix attached to greater than 50 copies of $\gamma\text{-TuRCs}$.

Katanin

A microtubule accessory protein named after the Japanese word for "sword" that severs microtubules.

MAPs (Microtubule-Associated Proteins)

Proteins that bind along the sides of microtubules to stabilize them against disassembly, suppressing catastrophe frequency and enhancing growth rate.

MAP2

A microtubule-associated protein with a long projecting domain that cross-links microtubules into stable, widely spaced parallel bundles.

Tau

A microtubule-associated protein that binds microtubules at both its N- and C-termini with a short projecting loop, forming closely packed microtubule bundles.

XMAP215

A Xenopus microtubule-associated protein with a molecular weight of $215\,kDa$ that stabilizes microtubule plus ends and accelerates assembly.

Kinesin-13

A family of catastrophe factors that bind to microtubule ends and pry protofilaments apart, lowering the activation energy barrier to induce rapid disassembly.

Plectin

A cytoskeletal cross-linking protein that links microtubules to intermediate filaments.

Kinesin

A microtubule motor protein that hydrolyzes ATP at its N-terminal heavy chain motor domain to walk toward the plus end of microtubules, transporting cargo bound at its C-terminus.

Dynein

A minus-end directed microtubule motor protein composed of 2 or 3 heavy chains that uses ATP hydrolysis to walk toward the centrosome.

Chemotaxis

Cellular movement in a direction determined by a concentration gradient of a diffusible chemical signal, such as neutrophils crawling toward bacterial peptide signals.

Hereditary Spherocytosis (HS)

The most common hereditary hemolytic anemia in people of Northern European descent ($1/2,000$), characterized by spherical and fragile red blood cells that lyse easily due to defects in the erythrocyte membrane skeleton.

Erythrocyte Membrane Skeleton (EMS)

A spectrin-based submembrane cytoskeleton network that provides durability, stability, and flexibility to RBCs as they navigate tight capillary spaces ($2\text{--}3\,\mu\text{m}$).

Osmotic Fragility Test

A diagnostic centrifugation test for Hereditary Spherocytosis in which blood is placed in hypotonic saline; normal RBCs swell without rupturing, whereas fragile spherocytes lyse and release hemoglobin.

KLF1 (Krüppel-like factor 1)

An erythroid DNA-binding transcription factor containing 3 zinc finger domains that regulates erythrocyte membrane skeleton genes; mutations in KLF1 cause Hereditary Spherocytosis.

Nan Mouse

A mouse model for Hereditary Spherocytosis carrying a Glu to Asp mutation in zinc finger 2 of Klf1, resulting in anemic spherical RBCs, osmotic fragility, reduced hemoglobin, and massive splenomegaly.

Duchenne Muscular Dystrophy (DMD)

A severe X-linked recessive neuromuscular disease ($1/3,500$ male births) caused by frameshift mutations in the dystrophin gene resulting in complete absence of functional dystrophin protein, severe progressive muscle degeneration, loss of ambulation by age 12, and early death.

Becker Muscular Dystrophy (BMD)

A milder X-linked recessive muscular dystrophy ($1/18,000$ incidence) caused by in-frame dystrophin gene deletions that produce an altered or truncated dystrophin protein of abnormal size (e.g., $390\,kDa$).

Dystrophin ($Dp427$)

A $427\,kDa$ protein ($3,685$ amino acids, 79 exons) localized to the inner sarcolemma surface that anchors internal actin filaments to the extracellular matrix via the dystrophin-associated glycoprotein complex.

Pseudohypertrophy

A clinical hallmark of Duchenne Muscular Dystrophy characterized by enlarged calf muscles resulting from replacement of degenerated muscle tissue with adipose and fibrous connective tissue.

Gower Sign

A physical diagnostic maneuver in DMD where a child uses hands and knees to "walk" hands up the legs to stand up due to weakened pelvic and lower limb muscles.

Complex Repetitive Discharges (CRDs)

Abnormal, spontaneously firing action potentials detected via electromyography (EMG) that serve as an indicator of muscle membrane instability in dystrophinopathies.

Retinal Dystrophin ($Dp260$)

A $260\,kDa$ endogenous isoform of dystrophin expressed primarily in the retina containing an internal actin-binding domain in its spectrin repeats; driven by a distinct promoter, it serves as a non-immunogenic gene therapy target to rescue DMD in skeletal muscle.