Cell Biology: Endomembrane System

Endomembrane System

• Also known as the secretory pathway, where proteins move from the ER to the Golgi to the outside of the cell.

Endoplasmic Reticulum (ER)

• The earliest secretory pathway organelle, consisting of a system of membranes that enclose a space (lumen) separated from the cytosol.
• ER has two sub-compartments: Smooth ER and Rough ER.

Smooth ER

• Synthesizes steroid hormones, not proteins.
• Stores calcium ions that trigger muscle contractions.
• Detoxifies alcohol and liver cells known as “barbiturates”.

Rough ER

• Studded with ribosomes.
• Synthesizes secretory pathway proteins and lipids.
• Site of protein folding, processing, and modification.
• Translates proteins made in the ER on ribosomes attached to the RER.

Protein Translation

• Proteins made in the ER are translated on ribosomes attached to the RER.
• Examples: secreted proteins (hormones and neurotransmitters), transmembrane proteins, and soluble proteins (golgi, lysosomal, and vacuolar proteins).
• Proteins translated in the cytosol are made on "free" ribosomes floating in the cytosol.
• Cytosolic proteins include enzymes, cytoskeletal proteins, and other soluble proteins.

ER Protein Co-translation and Translocation

• SRP (signal recognition particle) plays a crucial role in recognizing the signal sequence of the protein being translated.
• Translation begins on free ribosomes, then the protein complex moves to the ER membrane.
• Signal peptidase cleaves the signal sequence, allowing the protein to enter the ER lumen and fold with the help of chaperones.

ER Protein Post-translational Translocation

• Some proteins are fully synthesized in the cytosol and then transferred to the ER.
• These proteins still require a signal sequence to translocate.

ER Translocons

• Structurally similar across species, playing a crucial role in protein translocation.
• Examples: Sec61 (from chloroplast) is important for soluble and ER movement proteins.

Post-translational vs. Co-translational Translocation

• Protein translocation can occur either co-translationally (during protein synthesis) or post-translationally (after protein synthesis).

ER Membrane Protein Translocation

• Proteins have hydrophobic stop sequences that stay in the membrane.
• Proteins can be linked to the membrane with a GPI anchor.

Protein Folding and Modification

• Multitude of chaperones assist in folding proteins in the ER (e.g., BiP, GRP94, Calnexin, and calreticulin).
• PDI (protein disulphide isomerase) assists in forming disulphide bonds and is required for proper protein folding.
• Chaperones guide proteins to align correctly.
• Modification of proteins includes glycosylation.