Cell Biology: Microfilaments, Microtubules, and Cell Signaling

Comprehensive vocabulary flashcards covering the components, assembly kinetics, motor proteins, and regulatory mechanisms of microfilaments and microtubules, as well as GPCR-mediated intracellular signaling pathways and metabolic regulation.

Microfilaments

The smallest class of cytoskeletal fibers, composed of actin subunits organized into a right-handed double helix; they utilize ATP, assemble from many cellular locations, and maintain cell shape, motility, cortex structure, and cytokinesis.

G-actin

Globular monomeric actin that binds $Mg^{2+}$ and ATP under physiological conditions and polymerizes to form F-actin microfilaments.

F-actin

Filamentous actin assembled into a right-handed polarized double helix; its formation from G-actin does not require ATP hydrolysis, though hydrolysis occurs subsequently to alter polymerization kinetics.

Critical Concentration ($C_c$)

The concentration of unpolymerized G-actin at which the rate of subunit addition equals the rate of dissociation ($C_c = \frac{k_{\text{off}}}{k_{\text{on}}}$); net assembly occurs above $C_c$ and net disassembly occurs below it.

Treadmilling

A dynamic state occurring when free G-actin concentration is between the plus-end $C_c$ and minus-end $C_c$, resulting in continuous subunit addition at the plus end and loss at the minus end while filament length remains constant.

CapZ

A capping protein that binds the plus (barbed) end of microfilaments to prevent subunit addition when G-actin concentration is greater than or equal to $C_c$.

Tropomodulin

A capping protein that binds the minus (pointed) end of microfilaments to block subunit disassembly when G-actin concentration falls below the minus-end $C_c$.

Cofilin

An actin-binding protein that severs ADP-actin filaments into smaller fragments, accelerating depolymerization and generating new free ends and nuclei for actin recycling.

Profilin

A nucleotide exchange factor that accelerates the exchange of ADP for ATP on G-actin and remains bound to ATP-actin, ensuring it can only be added to the plus end.

Thymosin-$\beta 4$

A sequestering protein that binds ATP-G-actin and keeps it from polymerizing, lowering the available monomer pool without changing the cell's total actin concentration.

Formin

An actin nucleator and elongator activated by GTP-bound Rho; its FH1 domain loads profilin-ATP-actin while its FH2 domain adds monomers to the plus end to form straight, linear filaments and stress fibers.

Arp 2/3 Complex

An actin-related protein complex that binds to the side of an existing microfilament and nucleates the assembly of a new branch at an angle of $70^\circ$.

WASp

An adapter protein activated by GTP-bound Cdc42 that undergoes conformational unfolding to recruit the Arp 2/3 complex, driving branched actin polymerization in filopodia and immune cells.

WAVE

An adapter protein activated by GTP-bound Rac that recruits the Arp 2/3 complex to form branched microfilament networks in the lamellipodium at the leading edge of a migrating cell.

Rho

A small lipid-anchored G protein that activates formin to form linear microfilaments and activates Rho kinase and myosin to contract the trailing rear during cell migration.

Rho Kinase

A downstream kinase activated by Rho that phosphorylates integrins at the rear of a migrating cell, causing them to detach from the extracellular matrix.

Microtubules

The largest cytoskeletal filaments, consisting of rigid, hollow tubes composed of 13 protofilaments of $\alpha\beta$-tubulin heterodimers that originate at the MTOC and serve as tracks for organelle transport and chromosome movement.

$\alpha\beta$-Tubulin Heterodimer

The building block of microtubules; $\alpha$-tubulin carries a non-exchangeable, trapped GTP, whereas $\beta$-tubulin binds an exchangeable GTP that is hydrolyzed to GDP following polymerization.

Centrosome (MTOC)

The main microtubule organizing center in non-neuronal cells, containing a pair of mutually perpendicular centrioles (mother and daughter) surrounded by a ring of $\gamma$-tubulin that nucleates and caps minus ends.

Dynamic Instability

The behavior of individual microtubules alternating between periods of slow elongation and rapid shortening, determined by the presence or loss of the stabilizing GTP cap on $\beta$-tubulin.

Catastrophe

The sudden transition of an individual microtubule from elongation to rapid depolymerization (appearing as a peak on a growth graph) when GTP hydrolysis overtakes subunit addition and exposes curved GDP-protofilaments.

Rescue

The transition of a shrinking microtubule back to polymerization (appearing as a valley on a growth graph) when incoming GTP-tubulin restores a straight GTP cap.

Taxol

A drug that inhibits GTP hydrolysis on $\beta$-tubulin, preventing catastrophe and depolymerization, thereby locking microtubules in a stable state and arresting cells in mitosis.

MAP2

A microtubule-associated protein with a long projection arm that spaces microtubules relatively far apart near the cell body and in dendrites.

Tau

A microtubule-associated protein with a short arm that bundles axonal microtubules at close but regular intervals; its hyperphosphorylated or mutant forms (such as Tau P301S) aggregate into neurofibrillary tangles.

ApoE4

An HDL/cholesterol-carrying apolipoprotein variant containing two arginine residues that binds Tau, accelerates Tau aggregation, and constitutes the strongest genetic risk factor for Alzheimer's disease.

Kinesin

A two-headed plus-end-directed motor protein that hydrolyzes one ATP per $16\,\text{nm}$ step to carry vesicles and organelles outward (anterograde transport toward axon terminals).

Dynein

A compact, ATP-dependent motor protein that carries cargo toward the minus end of microtubules (retrograde transport toward the cell body and centrosome).

Kinesin-5

A specialized bipolar kinesin whose cargo is another microtubule; it crosslinks and slides antiparallel polar microtubules past each other to separate spindle poles during mitosis.

Kinesin-13

A non-motile kinesin that binds to microtubule ends and hydrolyzes ATP to pry protofilaments apart, actively promoting depolymerization during mitosis.

Endocrine Signaling

A systemic communication mode in which diffusible signaling molecules (hormones) travel through the bloodstream over long distances to act on distant target cells via cell-surface receptors.

Paracrine Signaling

Local intercellular signaling in which a secretory cell releases molecules that act on nearby target cells that are close but not in direct physical contact.

Autocrine Signaling

A form of signaling in which a cell secretes an extracellular ligand and expresses receptors for that same ligand, creating a positive feedback loop common in tumor growth and differentiation.

Signaling by Plasma Membrane-Attached Proteins

Direct contact signaling mediated by interactions between integral membrane proteins on adjacent cells without any intervening extracellular space.

G Protein-Coupled Receptor (GPCR)

A seven-pass transmembrane cell-surface receptor whose exoplasmic loops (E1–E3) bind specific extracellular ligands and whose cytosolic C3 loop acts as a GEF to activate heterotrimeric G proteins.

$$G\alpha_s$$

A stimulatory heterotrimeric G protein subunit that, when bound to GTP, dissociates from $G\beta\gamma$ and binds adenylyl cyclase to stimulate cAMP production.

$$G\alpha_i$$

An inhibitory heterotrimeric G protein subunit that, when activated by inhibitory GPCRs (such as adenosine or $PGE_1$ receptors), inhibits adenylyl cyclase and lowers cAMP levels.

$$G\alpha_o / G\alpha_q$$

Heterotrimeric G protein alpha subunits that activate phospholipase C, initiating the cleavage of membrane phospholipids into DAG and IP3.

Adenylyl Cyclase

A membrane-bound effector enzyme whose catalytic domains are brought together and activated by GTP-bound $G\alpha_s$ to convert ATP into the second messenger cAMP.

Phospholipase C

An effector enzyme activated by $G\alpha_o / G\alpha_q$ that cleaves membrane phospholipids into membrane-bound diacylglycerol (DAG) and soluble inositol 1,4,5-trisphosphate (IP3).

Inositol 1,4,5-Trisphosphate (IP3)

A water-soluble second messenger released from the membrane by phospholipase C that diffuses to the endoplasmic reticulum and opens ligand-gated $Ca^{2+}$ channels.

Diacylglycerol (DAG)

A hydrophobic second messenger produced by phospholipase C that remains anchored in the plasma membrane and acts together with cytosolic $Ca^{2+}$ to activate protein kinase C (PKC).

Calmodulin

A ubiquitous intracellular $Ca^{2+}$-binding protein containing four cooperative, allosteric $Ca^{2+}$-binding sites that modulates downstream target enzymes including PDE4A and GPK.

Nitric Oxide (NO)

A short-acting diffusible gas synthesized by NO synthase that passes through cell membranes without a receptor to directly activate intracellular guanylyl cyclase in smooth muscle cells, elevating cGMP.

Protein Kinase A (PKA)

A serine/threonine kinase made of two regulatory and two catalytic subunits; cooperative, allosteric binding of four cAMP molecules to the regulatory subunits releases active catalytic subunits to phosphorylate metabolic targets.

Glycogen Synthase (GS)

An enzyme responsible for incorporating UDP-glucose into glycogen; it is turned off via phosphorylation of a serine residue by PKA and PKC during the fight-or-flight response.

Glycogen Phosphorylase (GP)

An enzyme that cleaves glycogen into glucose 1-phosphate, activated via direct phosphorylation by glycogen phosphorylase kinase (GPK).

Glycogen Phosphorylase Kinase (GPK)

A 16-subunit enzyme complex ($\alpha_4\beta_4\gamma_4\delta_4$) activated to 50% by PKA phosphorylation of $\alpha/\beta$ subunits and to 50% by $Ca^{2+}$-calmodulin binding to the $\delta$ subunit, attaining 100% activity only when both are present.

Cholera Toxin

An enterotoxin that ADP-ribosylates $G\alpha_s$ to permanently block its intrinsic GTPase activity, locking adenylyl cyclase on, elevating cAMP, hyperactivating PKA, and keeping apical CFTR channels persistently open.

PDE4A

A cyclic nucleotide phosphodiesterase that degrades cAMP to 5'-AMP; its activity is doubled by $Ca^{2+}$-calmodulin to accelerate signal termination and is competitively blocked by caffeine.

$\beta$-Arrestin

A cytosolic regulatory protein that binds phosphorylated GPCRs to physically block G protein coupling (rapid desensitization) and target the receptor for endocytosis (slow desensitization).

Heterologous Desensitization

A desensitization mechanism in which elevated PKA phosphorylates all GPCRs that couple to $G\alpha_s$, broadly dampening cell sensitivity to multiple stimulatory hormones.

Homologous Desensitization

A negative feedback mechanism in which BARK ($\beta$-adrenergic receptor kinase) selectively phosphorylates only ligand-occupied $\beta$-adrenergic receptors, recruiting $\beta$-arrestin.