Protein Traffic, Endocytosis, and Cell Signaling

Vocabulary practice cards covering cellular transport pathways (inbound, outbound, vesicle formation, sorting signals, endocytosis) and cell signaling mechanisms (GPCRs, RTKs, second messengers, enzymatic cascades, and associated diseases).

Outbound pathway

The cellular transport route moving materials from inside the cell toward their destinations, including the cell surface and outside of the cell.

Inbound pathway

The cellular transport route that brings substances into the cell from the plasma membrane.

Phosphatidylserine (PS)

A phospholipid heavily enriched in the inner leaflet of the plasma membrane that directly contributes to membrane asymmetry.

Scramblase

An enzyme that nonspecifically shuffles phospholipids between both membrane leaflets to balance lipid quantities on each side.

Flippase

An enzyme that selectively moves specific phospholipids between membrane leaflets to establish and maintain membrane asymmetry.

Glycoprotein asymmetry

The phenomenon where carbohydrate chains attached to proteins in the ER and Golgi lumen exclusively end up on the extracellular surface of the plasma membrane, because membrane proteins do not flip orientation during transport.

KDEL sequence

A short amino acid retrieval sequence that directs resident ER lumen proteins back to the ER if they accidentally travel to the Golgi.

Mannose-6-phosphate (M6P)

A molecular phosphate tag added to sugar chains in the Golgi apparatus that directs lysosomal enzymes toward late endosomes and lysosomes.

Adaptor proteins (adaptins)

Proteins that recognize specific cargo receptors and connect them to coat proteins during vesicle formation.

Clathrin and COP proteins

Coat proteins that assemble into cage-like lattices around membranes, physically bending them outward to form a vesicle bud.

Dynamin

A protein that uses energy from GTP hydrolysis to pinch off the neck of a budding vesicle from the donor membrane.

Constitutive uptake (Pinocytosis)

A continuous, nonsignaled form of endocytosis ('cell drinking') in which the cell nonselectively internalizes extracellular fluid and dissolved solutes.

Receptor-mediated endocytosis

A selective internalization mechanism in which cell-surface receptors recognize specific ligands via a $4-6$ amino acid cytoplasmic hook (often exposing a tyrosine) to recruit internalization machinery.

Low-density lipoprotein (LDL)

A particle containing an interior core of cholesterol and cholesteryl esters enclosed by phospholipids and apolipoprotein B-100 (apoB) that transports cholesterol through the bloodstream.

Early endosome

An acidic sorting compartment ($\text{pH } 6.1-6.3$ maintained by V-type $H^+\text{-ATPases}$) where internalized cargo such as LDL dissociates from its receptor.

Recycling endosome

An endocytic compartment that packages freed cell-surface receptors and returns them back to the plasma membrane for reuse.

Lysosome

The cell's digestive and recycling compartment containing more than $100$ degradative enzymes operating at an acidic $\text{pH} < 5$.

Familial hypercholesterolemia

A hereditary disorder caused by absent or mutated LDL receptors that disrupts receptor-mediated endocytosis, preventing negative-feedback inhibition of cholesterol synthesis and leading to high blood cholesterol and atherosclerosis.

Lysosomal storage diseases

A group of disorders (such as Tay-Sachs, Gaucher, or Batten disease) caused by defects in specific lysosomal degradative enzymes, causing undigested material to accumulate and clog the lysosome.

Endocrine signaling

Long-distance signaling where specialized cells secrete hormones into the bloodstream to reach distant target cells, operating at low signal concentrations and requiring high receptor affinity.

Paracrine signaling

Local cell communication where signaling molecules diffuse through extracellular fluid to act on neighboring cells.

Synaptic signaling

Targeted neuronal signaling where electrical action potentials trigger the release of neurotransmitters across the synaptic cleft at very high local concentrations.

Contact-dependent signaling

A signaling mechanism requiring direct physical membrane-to-membrane contact between adjacent cells without releasing the ligand into the extracellular space.

Second messenger

A small intracellular molecule (such as $\text{cAMP}$ or $\text{Ca}^{2+}$) that rapidly relays and amplifies extracellular signals inside the target cell.

Adenylyl cyclase (AC)

A plasma membrane enzyme that synthesizes cyclic AMP ($\text{cAMP}$) and pyrophosphate ($\text{PP}_i$) from ATP.

Protein kinase A (PKA)

A kinase whose regulatory subunits dissociate from its catalytic subunits upon binding $\text{cAMP}$, freeing the catalytic subunits to phosphorylate target proteins.

Calmodulin (CaM)

An intracellular regulatory protein that binds free cytosolic $\text{Ca}^{2+}$, changing shape to activate CaM kinases and other downstream targets.

Protein kinase C (PKC)

An enzyme recruited to the plasma membrane and activated cooperatively by the second messengers diacylglycerol (DAG) and $\text{Ca}^{2+}$.

Kinase cascade

A chain reaction in which one activated protein kinase phosphorylates and activates another kinase downstream, achieving signal amplification.

Heterotrimeric G-protein

A membrane-associated molecular switch composed of $\alpha$, $\beta$, and $\gamma$ subunits that is inactive when GDP is bound to $\alpha$ and active when GTP replaces GDP.

Guanine nucleotide Exchange Factor (GEF)

A regulatory protein that activates G proteins by stimulating the dissociation of GDP so that GTP can bind.

GTPase-Activating Protein (GAP)

A regulatory protein that accelerates the intrinsic GTP hydrolysis of a G protein, rapidly turning it off into its GDP-bound state.

GDP Dissociation Inhibitor (GDI)

A regulatory protein that prevents GDP from leaving a G protein, stabilizing its inactive state.

Phospholipase C (PLC)

A membrane-associated enzyme activated by G proteins that cleaves the phospholipid $\text{PIP}_2$ into $\text{IP}_3$ and DAG.

Inositol 1,4,5-trisphosphate (IP3)

A water-soluble second messenger generated by PLC that diffuses through the cytosol to open calcium channels on the endoplasmic reticulum.

Diacylglycerol (DAG)

A hydrophobic, lipid-soluble second messenger generated by PLC cleavage of $\text{PIP}_2$ that stays in the plasma membrane to help activate PKC.

Cortical reaction

A calcium-triggered exocytosis of cortical granules in fertilized eggs that alters and elevates the fertilization envelope to block polyspermy.

Receptor tyrosine kinase (RTK)

A cell-surface receptor whose intracellular domain possesses tyrosine kinase activity, activated by ligand-induced dimerization and trans-autophosphorylation.

Trans-autophosphorylation

The mechanism where dimerized RTK subunits cross-phosphorylate tyrosine residues on each other, creating docking sites for intracellular signaling proteins.

Ras

A small, monomeric GTP-binding protein acting downstream of RTKs that switches between an inactive GDP-bound form and an active GTP-bound form.

MAP kinase cascade

A three-tiered kinase relay ($\text{MAPKKK} \rightarrow \text{MAPKK} \rightarrow \text{MAPK}$) initiated by active Ras that phosphorylates cytoplasm and nuclear targets to regulate cell division and growth.

McCune-Albright syndrome

A disease caused by a mutation that impairs a G protein's intrinsic GTPase activity, leaving it locked in the active GTP-bound state and leading to persistent signaling and precocious puberty.