Golgi Apparatus Structure and Function

Structure: The Golgi apparatus is a stack of flattened, membrane-bound compartments called cisternae. It consists of a cis face (closest to the ER), a trans face (farthest from the ER), and several cisternae in between. Vesicles bud off from the ER at the cis face and depart from the trans face for various destinations.

Endoplasmic Reticulum (ER): The source of vesicles that deliver proteins to the Golgi.
Golgi Vesicles: Transport proteins within the Golgi.
Vesicular Tubular Cluster (VTC): An intermediate compartment between the ER and Golgi, where vesicles fuse and cargo proteins are sorted.
Cis Golgi Network (CGN): The initial entry point of proteins into the Golgi.
Cis Cisterna: Early Golgi cisterna, where initial modifications are performed.
Medial Cisterna: Middle Golgi cisterna, where more modifications take place.
Trans Cisterna: Final Golgi cisterna, where the most sophisticated modifications occur.
Trans Golgi Network (TGN): The final processing and sorting station of the Golgi.
Secretory Vesicles: Vesicles that transport proteins out of the Golgi to the plasma membrane.
Plasma Membrane/Other Organelles: Destination for proteins after Golgi processing.

Protein Sorting, Modification, and Dispatch: The Golgi sorts, modifies, and packages proteins for secretion and delivery to various cell locations (e.g., other organelles or vesicles).

Secretory Cells: It's exceptionally prominent in secretory cells, like intestinal goblet cells, as it's a crucial site for carbohydrate synthesis in the form of glycoproteins and proteoglycans.

Complete Folding Required: Proteins must be properly folded before they exit the ER.
Glycosylation as a Folding Tag: Glycosylation (adding oligosaccharides to proteins) in the ER lumen marks proteins for folding and aids in their maturation process- Almost all proteins undergo this.

Re-Glycosylation: If a protein is still partially folded, a glucosyl transferase adds another glucose to assist in further folding attempts.
Chaperone Assistance: Repeated attempts to fold incorrectly are made.
Degradation: If folding is repeatedly unsuccessful, misfolded proteins are directed back to the ER for removal and degradation.
Export to Golgi: Correctly folded proteins are exported to the Golgi.

Chaperone Protein: Calnexin is a chaperone protein that recognizes incompletely folded proteins based on the terminal glucose and prevents their export from the ER until folding is complete.

Transmembrane Receptor Interactions: Soluble proteins interact with transmembrane receptors in the ER.
Exit Signals: Proteins need specific signals (exit signals) to efficiently exit the ER and be transported to the Golgi.
COPII Interaction: The coat protein COPII interacts with the cytosolic tail of the receptor to create a vesicle bud for transport.

Unknown in Many Cases: While the precise details aren't known for every protein, proteins like factors V and VIII are tagged based on mannose residues for ERGIC53 receptor binding.

Vesicle Budding: COPII-coated vesicles bud from the ER.
Coat Removal: The coat is quickly removed.
Homotypic Fusion: Vesicles fuse with each other to form VTCs.
Microtubule Movement: VTCs move along microtubules towards the Golgi.
Release from Receptor: Arrival at the Golgi leads to a change in pH that releases cargo from its receptors.
Cargo Discharge: Cargo is released from the receptors.

pH Regulation: The VTC regulates its own pH through membrane proteins that pump hydrogen ions.
Impact on Cargo: Lower pH changes the charge of some amino acids, triggering cargo release from the receptors.

Retrieval Mechanisms: The Golgi retrieves proteins that bud from the ER, and mistakes due to incorrect tagging, etc.
COPI Coats: COPI-coated vesicles bud from the VTC/Golgi and transport these proteins back to the ER.
KKXX Sequence: A cytosolic sequence (KKXX) on resident ER membrane proteins targets them for retrieval by COPI.

N-linked Glycosylation (ER): Oligosaccharides are added to asparagine (N) on the side-chains. Function including protein folding, and glucose trimming.
Early Cisternae Modification: Initial modifications (trimming of mannose residues) occurs.
Later Cisternae Modifications: Medial cisternae do more trimming + add N-acetyl-glucosamine and trans cisternae add galactose and N-acetylneuraminic acid.

Complex Modifications: Extensive modification, with hundreds of possibilities in oligosaccharide configuration and sequence.
Orderly Sequence: The process follows a specific order of sugar additions and removals; dependent on earlier steps.

O-linked: Addition of sugars to the hydroxyl groups of serine, threonine, or hydroxylysine. Initiated with N-acetyl galactosamine.
N-linked: Addition of oligosaccharides to asparagine.

Protein Markers: Used to signal folding completion, transport ER-Golgi, and Golgi sorting.
Protease Protection: Inflexible oligosaccharides prevent protein degradation.
Cell-Cell Recognition: Forms part of cell-cell recognition and adhesion systems.
Regulation: Oligosaccharides on receptors impact their activity in various cell types.

Vesicle Fusion: ER vesicles fuse to form VTCs and the CGN.
Cisternal Displacement: The CGN moves upwards and matures into the cis, medial, and then trans cisternae.
Enzyme Retrieval: Enzymes are retrieved through retrograde transport.
TGN Budding: Vesicles bud for dispatch or retrieval purposes from the TGN.