Molecular Signaling Within Neurons

Vocabulary flashcards covering chemical signaling types, receptor categories, G-protein cycles, second messengers, and calcium regulation within neurons.

Synaptic Signaling

A form of chemical communication in which neurotransmitters are released across a narrow synaptic cleft (approximately $20\,\text{nm}$) directly onto the receptors of a target cell.

Paracrine Signaling

A mode of chemical signaling where secreted molecules (such as neuropeptides, cytokines, neurotrophins, or nitric oxide) act locally by diffusing into the immediate vicinity of nearby target cells.

Endocrine Signaling

A long-distance signaling system where chemical messengers (hormones like cortisol or thyroid hormone) are secreted into the bloodstream to reach distant target cells throughout the body.

Signal Amplification

A phenomenon in signal transduction where a single upstream signaling molecule activates or generates multiple downstream effector molecules, ensuring a reliable physiological response despite counteracting noise.

Cell-Impermeant Molecules

A class of signaling molecules—including neurotransmitters, neurotrophins, interleukins, and peptide hormones like insulin—that cannot cross the plasma membrane and must bind to the extracellular domain of transmembrane receptors.

Cell-Permeant Molecules

Signaling molecules that can pass through the plasma membrane to act on intracellular receptors, including steroid hormones (cortisol, estrogen, testosterone), nitric oxide via membrane diffusion, and thyroid hormone via active transport.

Cell-Associated Molecules (CAMs)

Signaling proteins anchored to the extracellular surface of the transmitting cell that require direct physical contact with receptors on receiving cells, and which often mediate retrograde signaling and viral entry.

Channel-Linked Receptors

Transmembrane receptors (ionotropic receptors) that combine a ligand-binding domain and an ion pore into a single protein complex, opening directly upon ligand binding to allow ion permeation across the membrane.

Enzyme-Linked Receptors

Transmembrane receptors possessing an extracellular ligand-binding domain and an intracellular catalytic domain (most commonly a protein kinase) that phosphorylates intracellular targets upon activation.

Tyrosine Receptor Kinases (Trks)

A major class of enzyme-linked receptors that bind neurotrophins (e.g., NGF, BDNF, NT-3) on the cell exterior and phosphorylate intracellular tyrosine residues on target proteins.

G-Protein-Coupled Receptors (GPCRs)

Metabotropic transmembrane receptors featuring seven membrane-spanning domains that trigger cellular responses through intermediate heterotrimeric GTP-binding proteins.

Intracellular Receptors

Receptors located within the cytosol or nucleus that bind cell-permeant ligands and typically alter gene transcription, often requiring the dissociation of an inhibitory chaperone complex (such as heat shock proteins) to function.

Glucocorticoid Receptor (GR)

A cytosolic nuclear receptor that binds cortisol; upon ligand binding, it sheds an inhibitory heat shock protein (HSP), dimerizes, translocates into the nucleus, and activates RNA polymerase to stimulate transcription.

Thyroid Hormone Receptor (TR)

A nuclear receptor constitutively bound to DNA that acts as a transcriptional repressor in its basal state and transitions to a transcriptional activator upon binding actively transported thyroid hormone.

Heterotrimeric G-Proteins

GTP-binding proteins composed of $\alpha$, $\beta$, and $\gamma$ subunits that dissociate into an active $\alpha\text{-GTP}$ monomer and a $\beta\gamma$ complex following receptor-stimulated GDP-GTP exchange.

Monomeric G-Proteins

Single-subunit small GTPases (such as Ras) that relay signals from cell-surface receptors to downstream effectors (e.g., vesicle trafficking, cytoskeleton, transcription) using adaptor proteins and GEFs.

Guanine Nucleotide Exchange Factor (GEF)

An intracellular regulatory protein that promotes the activation of G-proteins by catalyzing the displacement of bound GDP with GTP.

GTPase Activating Protein (GAP)

A regulatory protein that accelerates the intrinsic GTP-hydrolyzing activity of G-proteins, converting bound GTP to GDP to terminate signaling.

$G_s$ Protein Pathway

A heterotrimeric G-protein pathway (e.g., downstream of $\beta$-adrenergic receptors) that activates adenylyl cyclase, increases cAMP production, activates PKA, and increases target protein phosphorylation.

$G_i$ Protein Pathway

An inhibitory heterotrimeric G-protein pathway (e.g., downstream of dopamine $D_2$ receptors) that inhibits adenylyl cyclase, decreases cAMP levels, and reduces protein phosphorylation.

$G_q$ Protein Pathway

A heterotrimeric G-protein pathway (e.g., downstream of mGluRs) that stimulates phospholipase C (PLC) to cleave $\text{PIP}_2$ into DAG and $\text{IP}_3$, leading to PKC activation and $Ca^{2+}$ release from the endoplasmic reticulum.

Adenylyl Cyclase

An enzyme activated by G-protein signaling that converts ATP into the intracellular second messenger cyclic AMP (cAMP).

Cyclic AMP (cAMP)

A ubiquitous second messenger derived from ATP that activates protein kinase A (PKA) and gates cyclic nucleotide-gated ion channels, and is degraded into AMP by cAMP phosphodiesterase.

Cyclic GMP (cGMP)

A second messenger produced from GTP by guanylyl cyclase that activates protein kinase G (PKG) and modulates cyclic nucleotide-gated channels, degraded into GMP by cGMP phosphodiesterase.

Phosphodiesterase

An enzyme responsible for degrading cyclic nucleotide second messengers by hydrolyzing cAMP to AMP or cGMP to GMP, thereby terminating their intracellular actions.

Cyclic Nucleotide-Gated Channel

An ion channel in the plasma membrane gated open by the direct intracellular binding of two cyclic nucleotides (cAMP or cGMP, but not both), resulting in a conformational change and ion flux.

Phospholipase C (PLC)

A membrane-associated effector enzyme that hydrolyzes the membrane phospholipid phosphatidylinositol bisphosphate ($\text{PIP}_2$) into diacylglycerol (DAG) and inositol 1,4,5-trisphosphate ($\text{IP}_3$).

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

A water-soluble second messenger generated by PLC that diffuses through the cytoplasm to bind and open $Ca^{2+}$ channels ($\text{IP}_3$ receptors) on the endoplasmic reticulum.

Diacylglycerol (DAG)

A lipid second messenger produced from $\text{PIP}_2$ by PLC that remains confined within the plasma membrane to activate protein kinase C (PKC).

Calmodulin

A primary calcium-binding effector protein that undergoes a conformational change upon binding free cytosolic $Ca^{2+}$, allowing it to bind and activate downstream target enzymes such as protein kinases and phosphatases.

Calcium Chelators (Buffers)

Intracellular calcium-binding proteins, such as calbindin and parvalbumin, that sequester free $Ca^{2+}$ ions to buffer and maintain resting cytosolic calcium concentrations without directly triggering signaling cascades.

Real-Time Single-Cell Calcium Imaging

An optical technique using engineered fluorescent biosensors to visualize neuronal activity in vivo by detecting changes in fluorescence ($\Delta F / F$) resulting from somatic $Ca^{2+}$ accumulation during action potentials.