Assignment
**Question:** Explain the path of a newly synthesized protein from the ribosome to
secretion out of the cell. Include the roles of ER, Golgi, and vesicles. (10 marks)
The Secretory Pathway of a Protein
Proteins that are secreted from a cell, such as hormones, enzymes, or antibodies, follow a
well-defined pathway called the secretory pathway. This pathway involves several
organelles and cellular processes that ensure the protein is properly synthesized,
modified, packaged, and exported. The key organelles involved are the ribosome,
endoplasmic reticulum (ER), Golgi apparatus, vesicles, and the plasma membrane.
1. Synthesis of the Protein at the Ribosome
- Protein synthesis starts in the cytoplasm when messenger RNA (mRNA), transcribed
from DNA, binds to a ribosome.
- If the protein is destined for secretion, it contains a signal peptide at its N-terminus. This
sequence is recognized by the signal recognition particle (SRP).
- The SRP temporarily halts translation and directs the ribosome to the rough
endoplasmic reticulum (RER) by binding to an SRP receptor on the ER membrane.
2. Translocation into the Rough Endoplasmic Reticulum (RER)
- Once docked, translation resumes, and the growing polypeptide chain is translocated
into the lumen of the RER through a translocon channel.
- Inside the RER:
• The signal peptide is usually cleaved off.
• The protein begins folding into its secondary and tertiary structures with the help of
molecular chaperones like BiP.
• Post-translational modifications start here, such as N-linked glycosylation, where
oligosaccharides are attached to asparagine residues.
• Disulfide bonds may form to stabilize the protein structure.
- Quality control occurs here — misfolded proteins are targeted for degradation.
3. Packaging into Transport Vesicles
- Properly folded and modified proteins are packaged into COPII-coated transport
vesicles, which bud off from the ER.
- These vesicles transport the protein to the cis face of the Golgi apparatus.
4. Processing in the Golgi Apparatus
- The Golgi apparatus consists of a series of flattened membrane-bound sacs called
cisternae.
- The protein enters at the cis-Golgi, moves through the medial-Golgi, and exits from the
trans-Golgi.
- During this journey, the protein undergoes:
• Further glycosylation (refinement and elaboration of sugar groups).
• O-linked glycosylation on serine and threonine residues.
• Sulfation, phosphorylation, and proteolytic cleavage, if necessary.
- The Golgi also plays a key role in sorting the protein by tagging it for delivery to the
correct cellular destination.
5. Sorting and Packaging into Secretory Vesicles
- In the trans-Golgi network (TGN), the modified protein is packaged into secretory
vesicles.
- Two types of secretion exist:
• Constitutive secretion — vesicles fuse with the plasma membrane continuously.
• Regulated secretion — vesicles store the protein and release it in response to specific
signals.
6. Vesicle Transport to the Plasma Membrane
- The secretory vesicles are transported along cytoskeletal elements (microtubules) using
motor proteins such as kinesin and dynein.
- Vesicles are directed towards specific sites at the plasma membrane.
7. Exocytosis — Secretion of the Protein
- When the vesicle reaches the plasma membrane, vesicle SNARE (v-SNARE) proteins
interact with target SNARE (t-SNARE) proteins on the membrane.
- This interaction causes vesicle docking and fusion.
- The vesicle membrane merges with the plasma membrane, releasing the protein into the
extracellular space via exocytosis.
Summary of Organelle Functions
Organelle/Structure Function
Ribosome Synthesizes polypeptide chain based on
mRNA
Signal Recognition Particle (SRP) Directs ribosome to RER
Rough Endoplasmic Reticulum Folding, initial glycosylation, quality
control
COPII Vesicles Transport protein to Golgi
Golgi Apparatus Further modifications, sorting, packaging
Secretory Vesicles Transport protein to plasma membrane
SNARE Proteins Dock and fuse vesicle with plasma
membrane
Plasma Membrane Secretes protein via exocytosis
Conclusion
The secretory pathway is a highly coordinated and regulated process involving multiple
organelles and precise molecular machinery. The protein is carefully synthesized,
modified, checked, packaged, and finally secreted outside the cell — ensuring the cell
functions efficiently and communicates effectively with its environment.
