Endoplasmic Reticulum

What is the endoplasmic reticulum (ER)?

A continuous system of flattened sacs and tubules (cisternae) forming an internal compartment called the lumen; its membrane is continuous with the nuclear envelope.

What is the main structural feature of the ER?

It consists of interconnected cisternae forming a continuous lumen.

What is the lumen of the ER continuous with?

The periplasmic space of the nuclear envelope.

What are the main functions of the ER?

Synthesis of new membranes, entry point for proteins, and detoxification of toxins and drugs.

What are the two main types of ER?

Rough ER (RER) and Smooth ER (SER).

What is the distinguishing feature of Rough ER?

It has ribosomes attached to its cytosolic surface.

What types of proteins are synthesized in the Rough ER?

Secretory, lysosomal, and membrane proteins.

What is the main function of the Smooth ER?

Synthesis of membrane lipids (phospholipids, steroids, triglycerides) and detoxification of organic molecules including alcohol.

What is the specialized form of Smooth ER found in muscle cells?

The Sarcoplasmic Reticulum (SR).

What is the function of the Sarcoplasmic Reticulum?

It stores Ca²⁺ ions which are released to trigger muscle contraction and reabsorbed for relaxation.

What sequence directs a protein to the ER?

An ER signal sequence consisting of eight or more hydrophobic amino acids.

What guides the ribosome to the ER membrane?

The Signal Recognition Particle (SRP) and the SRP receptor.

What is the function of the Signal Recognition Particle (SRP)?

It binds to the ER signal sequence and ribosome, pausing translation and directing them to the ER membrane.

What is the function of the SRP receptor?

It anchors the SRP–ribosome complex to the ER membrane.

What happens to proteins entering the ER?

They are either fully translocated into the lumen (soluble proteins) or partially embedded in the membrane (transmembrane proteins).

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

It opens the translocation channel, is cleaved by signal peptidase, and degraded.

Where do water-soluble proteins end up after synthesis?

Inside the ER lumen.

What are stop-transfer sequences?

Hydrophobic regions that halt translocation of a growing polypeptide, embedding part of it in the membrane.

What happens to the signal sequence in single-pass transmembrane proteins?

It is cleaved off after insertion into the membrane.

What is the orientation of a single-pass transmembrane protein in the membrane?

Amino terminus faces the lumen, carboxyl terminus faces the cytosol.

What initiates translocation in double-pass transmembrane proteins?

An internal start-transfer sequence.

What prevents full translocation of double-pass proteins?

A stop-transfer sequence halts movement, embedding both segments in the membrane.

What is the result of double-pass transmembrane protein insertion?

Both ends of the protein face the cytosol.

What chemical modifications occur in the ER?

Formation of disulfide bonds and glycosylation.

What is the role of disulfide bonds?

They stabilize proteins exposed to changing pH or degradative enzymes outside the cell.

What is glycosylation?

The covalent attachment of short oligosaccharide chains to asparagine residues in proteins.

What enzyme carries out glycosylation in the ER?

Oligosaccharyl transferase.

What are the functions of glycosylation?

Protects proteins from degradation, retains them in the ER until folded, helps guide them to target organelles, and mediates cell recognition.

What is the ER retention signal?

A carboxyl-terminal sequence of four amino acids that keeps proteins in the ER.

What happens to misfolded or unassembled proteins in the ER?

They are retained by chaperones until properly folded or degraded if refolding fails.

What role do chaperone proteins play?

They bind to partly folded chains and assist in proper folding.

What happens to irreversibly misfolded proteins?

They are transported to the cytosol and degraded by proteasomes.

How does cystic fibrosis relate to ER protein folding?

A misfolded but functional membrane transport protein is retained in the ER, leading to disease.

How are molecules transported from the ER to the Golgi complex?

By COPII-coated vesicles that bud off from ER exit sites.

What do Rab proteins do in vesicular transport?

They identify vesicles based on origin and cargo, ensuring delivery to the correct target.

What do tethering proteins do?

They mediate the initial recognition and docking between a vesicle and its target membrane.

What are SNARE proteins?

v-SNAREs on vesicles bind to t-SNAREs on target membranes, ensuring correct docking and catalyzing membrane fusion.

What happens after vesicle fusion?

The vesicle’s contents are delivered into the target organelle and its membrane merges with the organelle’s membrane.

Where does phospholipid, cholesterol, and ceramide synthesis occur?

In the smooth ER.

Where does phospholipid synthesis occur within the ER membrane?

On the cytoplasmic side.

What enzymes are involved in phospholipid synthesis?

Cytosolic enzymes such as acyl transferases and phosphatases.

What are flippases?

Enzymes that move phospholipids from one leaflet of the bilayer to the other.

What is the most active flippase in the ER membrane called?

Scramblase.

What phospholipids does scramblase move?

Choline-containing phospholipids.

How are phospholipids transported from the ER to other organelles like the Golgi?

By vesicle budding and fusion.

How are phospholipids transferred to mitochondria and peroxisomes?

By water-soluble phospholipid-exchange proteins.