The Golgi apparatus plays a vital role in processing and sorting proteins, lipids, and polysaccharides to their final destinations. The following pathways and mechanisms are key to its function:

1. Constitutive Secretory Pathway

• Proteins, lipids, and polysaccharides are transported from the Golgi to the plasma membrane without regulation.
• This pathway operates continuously in all cells and does not require specific signals.
• It supports the continuous secretion of proteins and incorporates newly synthesized lipids and proteins into the plasma membrane.
• Examples of proteins released through this pathway include:
  • Hormones from endocrine cells.
  • Neurotransmitters from neurons.
  • Digestive enzymes from pancreatic cells.

2. Regulated Secretory Pathway

• Some proteins are directed to secretory vesicles that store them near the plasma membrane.
• These proteins are released only in response to specific extracellular signals. For example:
  • A hormone or neurotransmitter may bind to receptors, triggering the release of vesicle contents.
  • Calcium ions (Ca²⁺) often mediate this signaling process.
• Maturation of secretory proteins occurs before their release. This includes:
  • Condensation (increased concentration of proteins).
  • Proteolytic processing (modifications like cleavage into active forms).
• Once matured, the vesicles remain near the plasma membrane until a signal causes them to fuse with the membrane and release their contents.

3. Lysosomal Pathway

• Proteins destined for lysosomes are sorted in the Golgi apparatus by a specialized mechanism:
  • These proteins are tagged with mannose-6-phosphate (M6P) residues.
  • The M6P tag is added through modifications of linked oligosaccharides shortly after the proteins enter the Golgi.
  • A specific receptor in the trans-Golgi network recognizes M6P residues and binds the tagged proteins.
  • The proteins are then packaged into transport vesicles and delivered to lysosomes.
• Lysosomal membrane proteins are targeted via signals in their cytoplasmic tails rather than M6P tags.

4. Retention of Proteins in the Golgi Apparatus

• Not all proteins are transported away; some remain in the Golgi.
• Proteins are retained within the Golgi due to specific signals, including:
  • Transmembrane domains, which prevent them from being packaged into vesicles for transport.
  • KXKXX sequences in the cytoplasmic tails of resident Golgi proteins. These sequences mediate retrieval of proteins from later compartments in the secretory pathway.

Key Notes on Secretory Protein Sorting

1. The constitutive secretory pathway ensures continuous delivery of proteins and membrane components to the cell surface, supporting normal cellular function.
2. The regulated secretory pathway enables cells to respond to external stimuli by releasing specific proteins at the right time.
3. The lysosomal pathway relies on M6P tagging for proper delivery of degradative enzymes and lysosomal membrane proteins.
4. Proteins that must remain in the Golgi apparatus have built-in retention or retrieval signals, ensuring they do not leave prematurely.

Overall Role of the Golgi Apparatus

• It acts as the central hub for protein processing and sorting.
• Proteins, lipids, and polysaccharides are chemically modified in the Golgi, such as glycosylation (addition of sugar chains) and phosphorylation.
• By using signal sequences and recognition mechanisms, the Golgi ensures precise delivery of cellular components to their correct locations.