Questions: Endoplasmic Reticulum and Golgi Apparatus

Question 1

A secretory protein enters the rough ER lumen after synthesis. What is the first major covalent modification it typically undergoes inside the ER?

• A. Phosphorylation by a Golgi-resident kinase
• B. Proteolytic cleavage in the trans-Golgi network
• C. N-linked glycosylation in the ER lumen
• D. Sorting into clathrin-coated vesicles at the plasma membrane

Answer: (C)

N-linked glycosylation — the attachment of a preformed oligosaccharide to asparagine residues — begins in the rough ER lumen as the protein is being synthesized. This is one of the earliest and most characteristic modifications in the secretory pathway. Phosphorylation and clathrin-coated vesicle sorting occur later in the Golgi (especially the trans-Golgi network), and proteolytic cleavage of signal peptides occurs at the ER membrane, not within the lumen of the Golgi.

Question 2

Most proteins synthesized by a eukaryotic cell is expected to pass through the endoplasmic reticulum and Golgi apparatus before reaching their final destination.

• T. True
• F. False

Answer: False

Only proteins destined for secretion, membrane insertion, or lysosomal delivery enter the ER/Golgi pathway. Proteins that function in the cytosol, nucleus, mitochondria, chloroplasts, or peroxisomes are synthesized on free (unattached) ribosomes and are imported post-translationally into their target compartments via dedicated translocators — bypassing the ER and Golgi entirely. The decision point is whether the nascent polypeptide contains a signal sequence that targets it to the ER membrane.

Question 3

What is the key functional difference between rough ER and smooth ER, and what structural feature reflects this difference?

Model answer: Rough ER is studded with ribosomes on its cytoplasmic face and specializes in synthesizing and processing membrane and secretory proteins (including folding and N-linked glycosylation). Smooth ER lacks ribosomes and instead specializes in lipid and steroid synthesis, calcium storage, and detoxification of drugs and metabolites. The presence or absence of membrane-bound ribosomes is the structural feature that directly reflects these different functions.

The ribosome-studded appearance of rough ER (giving it a 'rough' look under electron microscopy) is not decorative — those ribosomes are actively threading newly synthesized proteins into the ER lumen or membrane. Smooth ER's lack of ribosomes frees its membrane for the lipid-synthesis enzymes embedded within it. Cells with high secretory activity (e.g., pancreatic acinar cells) are dominated by rough ER; cells that synthesize steroids (e.g., adrenal cortex cells) have abundant smooth ER.