G-Protein-Coupled Receptors (GPCRs) and Cellular Signaling

Comprehensive vocabulary flashcards covering the structure, activation mechanisms, toxins, and downstream signaling cascades (cAMP and inositol phospholipid pathways) of G-protein-coupled receptors (GPCRs).

G-Protein-Coupled Receptors (GPCRs)

The largest family of cell-surface receptors, which mediate cellular responses to diverse signaling molecules (including proteins, fatty acids, hormones, and neurotransmitters) and serve as the target for approximately one-third of all known drugs.

Seven-Pass Transmembrane Receptor

The structural design characteristic of all GPCRs, consisting of a single polypeptide chain that threads through the plasma membrane $7$ times, with an extracellular N-terminus and an intracellular C-terminus that interacts with downstream effectors.

Trimeric G Protein

A membrane-associated signaling protein complex composed of three subunits ($\alpha$, $\beta$, and $\gamma$), two of which are tethered to the plasma membrane by short lipid tails, that couples GPCR activation to intracellular targets.

$\alpha$ Subunit (G Protein)

The subunit of a trimeric G protein that binds GDP in its inactive state, exchanges GDP for GTP upon GPCR stimulation, and possesses intrinsic GTPase activity to hydrolyze GTP back to GDP to turn itself off.

$\beta\gamma$ Complex

The dimeric signaling component of a G protein that can dissociate from or remain bound to the $\alpha$ subunit upon activation to regulate specific downstream target proteins, such as opening $\text{K}^+$ channels in heart pacemaker cells.

Intrinsic GTPase Activity

The self-inactivating enzymatic function of the G protein $\alpha$ subunit that hydrolyzes bound GTP into GDP, determining the lifespan of the active state and shutting off signal transmission.

Cholera Toxin (Vibrio cholera)

A bacterial toxin that modifies the G protein $\alpha$ subunit so it can no longer hydrolyze GTP, locking the G protein in an active state that stimulates a continuous outflow of $\text{Cl}^-$ and water into the gut, causing lethal dehydration unless replaced.

Pertussis Toxin (Bordetella pertussis)

A bacterial toxin from lung-colonizing bacteria that modifies the $\alpha$ subunit to disable the G protein, locking it permanently in an inactive GDP-bound state and stimulating severe coughing.

Adenylyl Cyclase

A membrane-bound target enzyme activated by a G protein $\alpha$ subunit that catalyzes the conversion of ATP into cyclic AMP ($\text{cAMP}$).

Cyclic AMP ($\text{cAMP}$)

A diffusible second messenger synthesized from ATP by adenylyl cyclase that activates cyclic AMP-dependent protein kinase (PKA).

Cyclic AMP Phosphodiesterase

An intracellular enzyme that degrades cyclic AMP into AMP through hydrolysis; its inhibition by substances such as caffeine maintains high cellular $\text{cAMP}$ levels.

Protein Kinase A (PKA)

A kinase normally held inactive in a complex; upon binding $\text{cAMP}$, it undergoes a conformational change that unleashes its active catalytic subunits to phosphorylate intracellular proteins and nuclear transcription regulators.

Phospholipase C (PLC)

A membrane-bound enzyme activated by a G protein ($\text{G}_q$) that cleaves an inositol phospholipid in the plasma membrane into two second messengers: $\text{IP}_3$ and DAG.

Inositol 1,4,5-Trisphosphate ($\text{IP}_3$)

A water-soluble second messenger generated by phospholipase C that diffuses through the cytosol and binds to ligand-gated $\text{Ca}^{2+}$ channels in the endoplasmic reticulum (ER) membrane, causing $\text{Ca}^{2+}$ release.

Diacylglycerol (DAG)

A lipid second messenger produced by phospholipase C cleavage that remains embedded in the plasma membrane and acts together with released $\text{Ca}^{2+}$ to recruit and activate protein kinase C (PKC).

Protein Kinase C (PKC)

An intracellular enzyme that requires binding to both membrane-bound DAG and cytosolic $\text{Ca}^{2+}$ to become fully active, subsequently phosphorylating specific target proteins depending on the cell type.

Calmodulin

A calcium-responsive protein found in the cytosol of all eukaryotic cells that binds $\text{Ca}^{2+}$, changes its conformation, and wraps around target proteins to alter their biological activity.

CaM-Kinases

$\text{Ca}^{2+}$/calmodulin-dependent protein kinases that become activated upon binding calmodulin; they regulate vital processes including learning and memory in the mammalian brain.

Adrenocorticotropic Hormone (ACTH) Response

A hormonal response mediated by cyclic AMP in which ACTH targets the adrenal gland to stimulate the secretion of cortisol.