The ER and secretory pathway

Question 1

Give an overview of the endoplasmic reticulum and secretory pathway

Answer 1

• Endoplasmic reticulum is continuous with the nuclear membrane/ envelope.
• Reticulum = “little net” in Latin
• Continuous network of tubules forming a net

Question 2

What is the function of the nuclear lamina?

Answer 2

network of proteins that lines the inside of the nuclear envelope, has a role in maintaining the structure of the nucleus. Nuclear lamina proteins are involved in gene regulation and transcription.

Question 3

Describe the structure of ER

Answer 3

• Single-membrane compartment consisting of a continuous network of tubular and flat vesicular structures in the cytoplasm- “little net”.
• Space inside is connected with the space between the two membrane surfaces of the nuclear membrane- continuous with the nuclear envelope.
• Two parts with different functions: granular/rough ER (ribosomes attached for the translation and folding of new proteins) and agranular/smooth ER (synthesis of lipids and detoxication of certain drugs and toxins by cytochrome P450 enzymes).

Question 4

Describe the functions of the ER

Answer 4

• Protein synthesis
• Glycosylation
• Ca2+ sequestration
• Detoxification by cytochrome P450 enzymes
• Folding and assembly and multi-protein complexes
• Lipid synthesis (cholesterol, phospholipids)

Question 5

Compare and contrast RER to the SER

Answer 5

On the Table

Question 6

Describe co-translational protein targeting to the ER.

Answer 6

1. mRNA associates with ribosome in the cytoplasm, scans from the initiation point.
2. If protein is destined for secretion, 20 amino acids will be the first distinct in structure and are hydrophobic called a signal sequence (proteolysis).
3. Synthesis thereafter stalls until the signal peptide has formed a complex with SRP (signal recognition particle).
4. The SRP associates with the ribosome so synthesis can continue, it guides the ribosome to a receptor on the surface of the ER membrane and allows it to bind to SRP receptor.
5. This binds the first part of the peptide, RNA ribosome to the ER guiding it to a channel called the translocation complex
6. As synthesis continuous the peptide can then be released/cleaved off into the lumen by the enzyme signal peptidase.
7. GTP used for free energy

Question 7

Describe insulin and protein modification

Answer 7

• Helps lower blood sugar.
• Made in beta cells in the islets of Langerhans.
• Signal sequence is cleaved to form proinsulin. Disulphide bridges (bonds) form between cysteine amino acids between chains of amino acids, here the protein is forming its final 3D structure.
• Protein modification only takes place in the lumen of the ER. Cytoplasmic proteins do not have disulphide bonds, only the enzymes that catalyse their formation only exist in ER.
• Proteolysis occurs, and the C peptide is removed to form a mature peptide.
• Proteolysis (signal peptide)
• Disulphide bond formation
• Glycosylation
• Deglycosylation
• Protein folding and assembly (tertiary and quaternary structure)

Question 8

Describe the structure and function of the golgi apparatus

Answer 8

• Single-membrane compartment consisting of 4 to 8 stacked layers of thin, flat, enclosed vesicles (cisternae) lying near one side of the nucleus.
• Three networks: cis (first cisternae structure, closer to nucleus), medial and trans compartments (final structure, closer to cell membrane).

Question 9

Where do vesicles transport proteins?

Answer 9

Vesicles transport proteins:
• From the Golgi apparatus to lysosomes and the plasma membrane.
• From the plasma membrane to lysosomes.
• From endosomes to the plasma membrane.