Golgi Apparatus and Protein Sorting
Golgi Apparatus Overview
- Receives proteins and lipids from the ER.
- Sorts and modifies these molecules and dispatches them to other destinations.
- Destinations include: cell surface, endosomes, lysosomes, and secretory granules.
COPII Coat: Involved in transport from the ER to the Golgi.
- Structure includes Sec13-31 and Sec23-24.
COPI Budding Mechanism
- ARF (ADP-ribosylation factor) plays a crucial role.
- ARF-GEF (Guanine nucleotide exchange factor) facilitates the exchange of GDP for GTP on ARF.
- Coatomer is involved in the COPI coat assembly.
- ARF-GAP stimulates GTP hydrolysis.
ER Protein Salvage
- ER resident proteins are prevented from getting into COPII buds via:
- Anchoring in the ER.
- Steric hindrance.
- Lost ER proteins are salvaged by a C-terminal -KDEL sequence recognized by a KDEL receptor.
- -KDEL sequence is both necessary and sufficient for ER retrieval.
- ER resident proteins are prevented from getting into COPII buds via:
Golgi Functions
- Sorting of ER-derived proteins and processing of
glycans. - Remodeling the lipid bilayer, involving phospholipids, sphingolipids, and cholesterol.
- Sorting of ER-derived proteins and processing of
Cargo Transport Through the Golgi: How are cargo transported while modifying enzymes stay put?
Cell-Free Transport Assays: Used to study Golgi function
- Example: Using mutant CHO cell lines lacking GlcNAc transferase.
COPI Vesicles: Carry retrograde cargo
Models of Golgi Transport
- Cisternal Maturation: Cisternae mature from cis to trans.
- Stable Compartments: Enzymes are in stable compartments.
Lysosomal Enzyme Biogenesis
- Involves mannose-6-phosphate (M6P) modification and M6P receptors (M6PR).
GGA Adaptor
- Involved in the transport of lysosomal enzymes.
- Ligand-receptor-adaptor-clathrin complex: (X)M6P - M6PR - GGA - clathrin.
I-Cell Disease: Related to defects in lysosomal enzyme targeting.
Tay-Sachs Disease: Associated with enlarged lysosomes due to a loss of β-hexoseaminidase.