Endoplasmic Reticulum

Endoplasmic Reticulum – A brief overview
The endoplasmic reticulum is a complex system of membrane channels and sacs. It is made up of two regions. In the rough endoplasmic reticulum, ribosomes are associated with the outer surface of the ER membrane. The proteins made by these ribosomes are deposited into the central cavity (lumen) of the ER for further biochemical processing. The proteins transported into the lumen will eventually make their way into the lysosomes and peroxisomes, become incorporated into the plasma membrane, or will be secreted out of the cell.

Endoplasmic Reticulum – Quality Control
It is not at all uncommon for proteins in the ER lumen to become incorrectly folded or to be improperly assembled. Quality control activities ensure that proteins are properly produced and processed by the rough ER. Biochemists have discovered that proteins in the ER lumen experience both primary and secondary quality checks. Primary quality control operations monitor general aspects of protein folding. Secondary quality control operations oversee posttranslational processing unique to specific proteins.

Remarkably, the ER quality control mechanism has the ability to discriminate between misfolded proteins and partially folded proteins that appear to be misfolded but are in fact in the process of adopting their intended structures. If the quality control operations could not efficiently make this distinction, it would be catastrophic to the viability of the cell.

The ER quality control systems utilize information contained within oligosaccharides as sensors to monitor the folding status of proteins. The process begins when the ER’s machinery attaches an oligosaccharide (Glc3Man9GlcNAc2) to newly made proteins after they have been manufactured by ribosomes and translocated into the lumen of the ER. Inside the ER, two Glc units are trimmed from the oligosaccharide to form Glc1Man9GlcNAc2. This modified attachment signifies to the ER’s machinery that it is time for chaperones to assist the protein with folding.

Once folding has been completed, the remaining Glc residue is cleaved to generate the oligosaccharide Man9GlcNAc2. This attachment tells the ER’s quality control system to scrutinize the newly folded protein for any defects. If improperly folded, the ER’s machinery reattaches Glc to the oligosaccharide and sends the protein back to the chaperones to be refolded.

After this, the ER machinery removes a Man group to generate Man8GlcNAc2. This marker subsequently triggers the ER machinery to send the protein to the Golgi apparatus. If any proteins with the Man8GlcNAc2 attachment are detected as being misfolded, they are targeted for degradation. Thus, if the structure of the bound oligosaccharide does not match the expected state of the protein, either a recycling or a destruction sequence will be triggered. Proteins targeted for destruction are shuttled into the cell’s cytoplasm and coated with the protein ubiquitin, where it is destroyed by the proteasome.

Endoplasmic Reticulum – Conclusion
Only a designer who exercises thought and foresight could be so deliberate as to orchestrate effective quality control procedures. The cell’s quality assurance systems logically compel the conclusion that life’s chemistry emanates from the work of an intelligent designer.