Getting proteins to the ER and beyond

Post-translational targeting

Proteins fully translated in the cytosol are later delivered to destinations such as nucleus, mitochondria, and peroxisomes.

Co-translational targeting

Ribosome is directed to the ER while translation occurs, delivering proteins into/through the ER membrane.

Nuclear localization signal (NLS)

Short stretch of basic residues that directs proteins to the nucleus via importins.

Peroxisomal SKL sequence

C-terminal tripeptide that targets proteins to peroxisomes.

Mitochondrial targeting sequence

N-terminal amphipathic helix recognized by mitochondrial chaperones.

ER roles

Protein synthesis (co-translational), protein folding, quality control, and lipid/steroid synthesis.

ERAD function

Degrades misfolded or improperly assembled ER proteins to maintain quality control.

CFTR ΔF508 mutation consequence

Causes misfolding and ERAD-mediated degradation, preventing channel delivery to the plasma membrane.

Viral hijacking of ERAD

Some viruses redirect MHC proteins for degradation to avoid immune detection.

COPII vesicles

Carry properly folded and glycosylated proteins from ER to Golgi.

Golgi processing

Carbohydrate trimming and modification; addition of mannose-6-phosphate to lysosomal proteins.

Mannose-6-phosphate role

Tags proteins for delivery to lysosomes via M6P receptors.

Rabs as identity labels

Small GTPases ensuring vesicles fuse only with correct target membranes via GDP/GTP cycling.

Clathrin-mediated endocytosis

Major pathway for internalizing receptors and ligands from plasma membrane.

LDL receptor pathway

Receptor binds LDL, internalizes it via clathrin pits, then releases LDL in acidic endosomes.