Endoplasmic Reticulum

What is the endoplasmic reticulum (ER)?

The ER is a continuous system of flattened sacs and tubules called cisternae, forming an internal compartment called the lumen that is continuous with the nuclear envelope.

What are the main functions of the ER?

Major site of new membrane synthesis, entry point for proteins destined for other organelles or the ER, and detoxification of toxins and drugs.

What are the two types of endoplasmic reticulum?

Rough Endoplasmic Reticulum (RER) and Smooth Endoplasmic Reticulum (SER).

What distinguishes RER from SER?

RER has ribosomes on its surface and synthesizes secretory, lysosomal, and membrane proteins. SER lacks ribosomes and synthesizes lipids and detoxifies molecules.

What is the function of the sarcoplasmic reticulum (SR)?

In muscle cells, SR stores Ca²⁺ and releases it to trigger contraction; it reabsorbs Ca²⁺ for relaxation.

What is the ER signal sequence?

A segment of eight or more hydrophobic amino acids that directs a protein to the ER.

What guides the ER signal sequence to the ER membrane?

The signal-recognition particle (SRP) binds to the signal sequence and ribosome, directing them to the SRP receptor on the ER membrane.

What are the two main types of proteins transferred into the ER?

1. Water-soluble proteins (fully translocated into the lumen). 2. Transmembrane proteins (partly translocated and embedded in the membrane).

What happens to the ER signal sequence of water-soluble proteins?

It opens the translocation channel, is cleaved off by signal peptidase, and degraded; the protein is released into the ER lumen.

How are single-pass transmembrane proteins formed?

Transfer halts at a stop-transfer sequence; the protein is inserted into the bilayer, with the N-terminus in the lumen and the C-terminus in the cytosol.

How are double-pass transmembrane proteins formed?

An internal start-transfer sequence initiates translocation, and a stop-transfer sequence halts it; both sequences embed in the bilayer, leaving both termini in the cytosol.

What are disulfide bonds, and why are they important?

Disulfide bonds stabilize protein structure, especially for proteins that function in variable pH or degradative environments.

What is glycosylation?

The covalent attachment of short oligosaccharide side chains to asparagine residues in proteins, aiding folding, protection, and targeting.

What enzyme performs glycosylation in the ER?

Oligosaccharyl transferase (a membrane-bound enzyme).

What functions do oligosaccharide side chains serve?

They protect proteins from degradation, help folding, guide targeting, and assist in cell recognition.

What is the ER retention signal?

A four-amino-acid sequence at the C-terminus that retains proteins in the ER.

What ensures only properly folded proteins exit the ER?

Chaperone proteins assist folding; misfolded proteins are retained or degraded if refolding fails.

What disease is caused by misfolded ER proteins retained in the ER?

Cystic fibrosis – due to misfolding of a plasma membrane transport protein that would otherwise function normally.

What coats vesicles that transport molecules from the ER to the Golgi?

COPII-coated vesicles.

How do vesicles recognize their target membranes?

Rab proteins identify vesicles, tethering proteins mediate initial contact, and SNAREs ensure specific docking and fusion.

What happens during vesicle fusion?

v-SNAREs on vesicles bind t-SNAREs on targets, causing membrane coalescence and fusion, delivering cargo to the organelle.

Where does synthesis of phospholipids occur?

On the cytoplasmic side of the smooth ER membrane, using cytosolic enzymes and substrates.

What enzyme moves phospholipids between membrane layers?

Flippases (scramblases move both sides; flippases maintain asymmetry).

How are ER-synthesized phospholipids transferred to other organelles?

By vesicle budding (to Golgi, lysosomes, plasma membrane) or water-soluble phospholipid-exchange proteins (to mitochondria, peroxisomes).