Cell Biology: Intracellular Membrane Traffic, Signaling, Cytoskeleton, and the Cell Cycle

Vocabulary review flashcards covering intracellular trafficking, cell signaling pathways, cytoskeletal filament dynamics, and cell cycle control mechanisms from Chapters 13, 15, 16, and 17.

Exocytosis

A process that releases material to the outside of the cell via vesicle fusion with the plasma membrane.

Endocytosis

A process in which the plasma membrane folds inward to capture and bring external material into endosomes.

Lumen

The internal space enclosed within an organelle or transport vesicle that holds transported cargo.

COPII

A vesicle coat protein that mediates anterograde transport from the ER to the Golgi; Sar1-GTP recruits Sec23/Sec24 for cargo selection and Sec13/Sec31 to assemble the outer cage.

COPI

A vesicle coat protein that carries cargo in a retrograde direction from the Golgi back to the ER and between Golgi cisternae.

Clathrin

A coat protein composed of three-legged triskelions (three heavy and three light chains) that uses adaptor proteins to transport material from the plasma membrane to endosomes and from the trans-Golgi network (TGN) to endosomes.

Dynamin

A GTPase that wraps around the neck of an invaginating clathrin-coated vesicle and hydrolyzes GTP to pinch the vesicle off from the donor membrane.

Phosphoinositides (PIPs)

Phosphorylated phosphatidylinositol headgroups that act as localized identity markers on organelle membranes to recruit specific trafficking proteins.

Rab GTPases

Small GTPases that confer membrane identity; active Rab-GTP recruits tethering proteins to capture incoming transport vesicles, with Rab5 marking early endosomes and Rab7 marking late endosomes.

SNARE Mechanics

The pairing of v-SNAREs on transport vesicles with t-SNAREs on target membranes into a four-helix bundle that draws the lipid bilayers close together to drive membrane fusion.

NSF

An ATPase that utilizes ATP hydrolysis to dissociate and recycle the four-helix SNARE complex after membrane fusion has occurred.

KDEL Sequence

A C-terminal peptide retrieval signal on soluble ER-resident proteins that binds KDEL receptors in the acidic Golgi to be packaged into COPI vesicles and returned to the neutral ER lumen.

O-Linked Glycosylation

The enzymatic addition of sugars directly to the oxygen atom of serine or threonine residues within the Golgi apparatus to enhance protein stability and protection.

Cisternal Maturation Model

A model of Golgi transport proposing that Golgi cisternae physically mature and migrate from the cis to the trans face while resident processing enzymes are continuously recycled backward in vesicles.

Vesicle Transport Model

A model of Golgi transport proposing that Golgi cisternae are long-lived, stationary compartments while transport vesicles shuttle cargo forward from one cisterna to the next.

Lysosomal Acid Hydrolases

Digestive enzymes enclosed within lysosomes that degrade cellular components at an optimal acidic pH of $4.5-5.0$, maintained by V-type $\text{H}^+$-ATPases.

Mannose-6-Phosphate (M6P)

A carbohydrate modification added to lysosomal enzymes in the Golgi apparatus that targets them for delivery to lysosomes; defects cause lysosomal storage diseases such as Tay-Sachs, Gaucher, and I-cell disease.

Contact-Dependent Signaling

An intercellular communication mechanism requiring direct membrane-to-membrane contact between signaling and target cells.

Paracrine Signaling

A form of cell signaling where locally secreted signal molecules act on nearby, neighboring target cells.

Endocrine Signaling

A long-range signaling mechanism in which specialized cells secrete hormones into the bloodstream to reach distant target cells throughout the body.

GPCR (G-Protein-Coupled Receptor)

A cell-surface receptor spanning the membrane with $7$ transmembrane segments; ligand binding activates an associated trimeric G protein by prompting its alpha subunit to exchange GDP for GTP.

cAMP / PKA Pathway

A signaling cascade in which active $\text{G}\alpha$ stimulates adenylyl cyclase to produce cAMP from ATP; cAMP then binds the regulatory subunits of PKA, freeing catalytic subunits to enter the nucleus and phosphorylate CREB.

$\text{IP}_3$ / DAG / $\text{Ca}^{2+}$ Pathway

A pathway in which active $\text{G}_q$ activates phospholipase C (PLC) to cleave $\text{PIP}_2$ into $\text{IP}_3$ and DAG; $\text{IP}_3$ triggers the opening of $\text{Ca}^{2+}$ channels in the ER, and the released $\text{Ca}^{2+}$ along with DAG activates Protein Kinase C (PKC).

GPCR Desensitization

The mechanism whereby GPCR Kinases (GRKs) phosphorylate active receptors to recruit arrestin, uncoupling the receptor from G proteins and promoting its internalization.

Receptor Tyrosine Kinases (RTKs)

Enzyme-coupled cell surface receptors that, upon ligand binding, form dimers and undergo cross-autophosphorylation on their cytoplasmic tyrosine residues.

Ras / MAP Kinase Cascade

A signaling pathway initiated when phosphorylated RTKs recruit Grb2 and the GEF Sos to load Ras with GTP, which successively activates Raf (MAPKKK), MEK (MAPKK), and ERK (MAPK) to control proliferation, differentiation, and survival.

Notch Signaling

A contact-dependent pathway in which Delta on one cell binds Notch on another, causing irreversible proteolytic cleavage that frees the Notch intracellular domain (NICD) to enter the nucleus during lateral inhibition.

Nitric Oxide (NO)

A dissolved gas that diffuses into vascular smooth muscle cells and activates guanylyl cyclase to increase cGMP, resulting in blood vessel relaxation and dilation.

Actin Filaments

Two-stranded helical cytoskeletal polymers of actin that drive cell locomotion, cell shape changes, and muscle contraction.

Microtubules

Hollow, cylindrical cytoskeletal filaments formed from $13$ parallel protofilaments of $\alpha\beta$-tubulin heterodimers that govern intracellular transport, cilia/flagella movement, and chromosome segregation.

Intermediate Filaments

Rope-like, flexible cytoskeletal polymers composed of staggered, antiparallel non-polar tetramers that provide high tensile strength and protect cells against mechanical stress.

Treadmilling

A steady-state dynamic of actin filaments where the rate of subunit addition at the fast-growing plus (+)/barbed end precisely equals the rate of subunit dissociation from the slower-growing minus (-)/pointed end.

Arp2/3 Complex

An actin-nucleating complex activated downstream of Rac1 that nucleates branched actin networks to push out the broad sheet-like membrane projections known as lamellipodia.

Formins

Actin-nucleating proteins activated by RhoA that promote the polymer assembly of long, parallel, unbranched actin bundles found in contractile stress fibers.

Dynamic Instability

The rapid switching of microtubules between phases of polymer growth and shrinkage; loss of the protective GTP cap on $\beta$-tubulin induces rapid depolymerization (catastrophe), whereas regaining it permits regrowth (rescue).

$\gamma$-Tubulin Ring Complex ($\gamma$-TuRC)

A ring-shaped protein scaffold located at the Microtubule Organizing Center (MTOC) / centrosome that serves as the nucleation site for new microtubules.

Kinesins and Dyneins

Microtubule motor proteins; kinesins generally step toward the filament plus (+) end, while dyneins move cargo toward the filament minus (-) end.

Keratins

A class of intermediate filaments present in epithelial tissues; mutations in keratin genes cause epidermolysis bullosa simplex, characterized by severe skin blistering.

Nuclear Lamins

Intermediate filament proteins that form a meshwork lining the inner nuclear membrane to provide structural support; mutations in their genes cause the premature aging condition Hutchinson-Gilford progeria.

LINC Complex

A mechanical bridge consisting of inner nuclear membrane SUN proteins and outer nuclear membrane KASH proteins that connects the nuclear envelope directly to the cytoskeleton.

Wee1 and Cdc25

Key regulatory enzymes acting on Cdks; Wee1 kinase adds an inhibitory phosphate to suppress Cdk activity, while Cdc25 phosphatase removes that phosphate to trigger Cdk activation.

Anaphase-Promoting Complex/Cyclosome (APC/C)

A ubiquitin ligase activated by Cdc20 that targets securin for destruction (allowing active separase to cleave cohesin rings for sister chromatid separation) and destroys M-cyclin to drive mitotic exit.

p53

A critical tumor suppressor protein stabilized by ATM/ATR kinases in response to DNA damage; it induces the CKI p21 to halt cell cycle progression for repair or directs the cell to undergo apoptosis if damage is irreparable.

Replicative Senescence

A state of permanent cell division arrest triggered by progressive telomere shortening, an attrition process that can be reversed or maintained by the enzyme telomerase.