Secretory Pathway: UPR, The Golgi and Lysosomes - Vocabulary Flashcards

Vocabulary flashcards covering key concepts from the lecture notes.

Unfolded Protein Response (UPR)

Cellular response to accumulation of unfolded/misfolded proteins in the ER; increases chaperones and proteases and decreases general protein synthesis to relieve ER stress.

Endoplasmic Reticulum (ER)

Membrane-bound organelle where protein folding and initial N-linked glycosylation occur; site of ER quality control (calnexin cycle).

Golgi apparatus

Stacked cisternae that modify, sort, and package proteins; organized into cis, medial, and trans zones with CGN and TGN.

COPII vesicles

Vesicles budding from the ER to the Golgi (anterograde transport) coated by COPII; involve Sar1–GTP and Sec23/24 and Sec13/31.

COPI vesicles

Retrograde transport from Golgi to ER and intra-Golgi; coatomer-coated vesicles that retrieve ER residents.

Clathrin-coated vesicles

Vesicles that sort cargo to the plasma membrane, lysosomes, or endocytosis; form with clathrin coats and adaptor proteins.

Clathrin triskelion

Three heavy chains and three light chains that assemble into a three-armed clathrin structure forming a basket around vesicles.

AP2 adaptor complex

Adaptor protein that binds phosphoinositides and cargo receptors at the plasma membrane to recruit clathrin for vesicle formation.

Phosphoinositides (PIPs)

Membrane lipids phosphorylated on inositol that define organelle identity and recruit adaptor proteins via specific binding.

Rab GTPases

Small GTP-binding proteins that control vesicle movement and targeting by recruiting tethering factors; cycle between GTP- and GDP-bound forms.

SNARE proteins

Family of proteins that mediate vesicle docking and fusion; v-SNAREs on vesicles and t-SNAREs on targets form a trans-SNARE complex; disassembled by NSF.

Dynamin

GTPase that forms a collar around the vesicle neck and uses GTP hydrolysis to sever the vesicle from the membrane.

ER-to-Golgi transport (anterograde)

Movement of cargo from the ER to the Golgi via COPII vesicles.

ER-Golgi intermediate compartment (ERGIC)

Vesicular tubular clusters that form after COPII vesicle budding; intermediate between ER and Golgi.

Mannose-6-phosphate (M6P)

Golgi-added carbohydrate tag that targets lysosomal enzymes to lysosomes via mannose-6-phosphate receptors.

Mannose phosphorylation

Addition of phosphate to mannose residues on lysosomal enzymes to create the M6P signal.

Mannose-6-phosphate receptor (MPR)

Receptor in the trans-Golgi network that binds M6P-tagged lysosomal enzymes and directs them to endosomes/lysosomes; recycled to Golgi.

KDEL retrieval signal

ER-resident soluble protein signal; binds KDEL receptor in Golgi and retrieves proteins back to the ER.

KKXX retrieval signal

ER-retention signal for membrane proteins; binds COPI and retrieves proteins back to the ER.

Endo H sensitivity

Assay distinguishing high-mannose (Endo H sensitive) from complex N-glycans (Endo H resistant) formed in the Golgi.

N-linked glycosylation

Attachment of an oligosaccharide to asparagine in the consensus sequence Asn-X-Ser/Thr in the ER; processed to complex glycans in the Golgi.

Calnexin cycle

ER quality-control cycle: glucosidases I/II trim glucose; calnexin binds monoglucosylated glycoprotein; UGGT reglucosylates if misfolded to re-enter the cycle.

Cystic fibrosis (ER quality control)

Mutant CFTR misfolds in the ER, is recognized by quality control and degraded, reducing its functional levels.

Golgi: cisternal maturation vs vesicle transport

Two models for Golgi function: vesicle transport moves cargo between stable cisternae; cisternae themselves mature and are retrogradely replenished.

Golgins

Cytosolic Golgi tethering proteins that capture transport vesicles by interacting with Rab proteins; fragmentation regulated during mitosis.

Lysosome

Digestive organelle with acidic lumen; contains hydrolytic enzymes and uses V-ATPases to maintain low pH; breaks down macromolecules for recycling.

Lysosomal enzyme sorting (M6P pathway)

Lysosomal enzymes are phosphorylated with mannose phosphate in the Golgi, bound by MPRs in the TGN, and delivered to endosomes/lysosomes; MPRs recycled.

Mannose-6-phosphate receptor recycling

MPRs return to the Golgi after delivering enzymes to endosomes/lysosomes, enabling multiple rounds of transport.

Lysosomal storage disorders (I-cell disease)

Enzyme mis-sorting due to failure to add M6P, causing enzymes to be secreted outside cells and buildup of material in lysosomes; severe symptoms.

Exocytosis

Process by which secretory vesicles fuse with the plasma membrane to release contents; lumen becomes extracellular; membrane proteins insert into PM.

Constitutive secretion

Default continuous secretory pathway where proteins are secreted non-stop; most secreted and membrane proteins use this route.

Regulated secretion

Secretory proteins stored in secretory granules and released in response to a specific signal (hormones, neurotransmitters).

Vesicle tethering, docking and fusion

Sequence of events: tethering by Rab effectors, docking via SNAREs, fusion forming a trans-SNARE complex; followed by SNARE disassembly by NSF.

Endocytosis and phagocytosis

Pathways for internalizing material from the plasma membrane; phagocytosis engulfs large particles; endocytosis forms endosomes.

Endosomes

Membrane-bound compartments that sort internalized material; early endosome matures to late endosome and fuses with lysosomes.

Signal sequence for ER targeting

N-terminal ER signal peptide directs ribosome to ER via SRP for co-translational translocation.

Peroxisomal targeting sequence (PTS1)

C-terminal signal that directs proteins to peroxisomes; commonly SKL motif.

Nuclear localization signal (NLS)

A sequence that directs proteins to the nucleus by interacting with nuclear transport machinery and Ran gradient.