Endoplasmic Reticulum (ER) in Eukaryotic Cells

Overview

The ER is the most extensive membrane system in eukaryotic cells.
Proteins transported to the Golgi apparatus, endosomes, lysosomes, and the cell surface must first enter the ER from the cytosol.

Polyribosomes:
- Two populations in the cytosol: free ribosomes and membrane-bound ribosomes.
- Membrane-bound ribosomes attach to the ER membrane to translate proteins translocated into the ER.
Rough Endoplasmic Reticulum:
- Regions of the ER coated with ribosomes.
Protein Movement:
- Two types:
  - Water-soluble proteins: Cross the ER membrane completely, releasing into the lumen.
  - Transmembrane proteins: Partially cross and embed in the membrane.

Signal Sequence:
- Directs proteins to the ER, consisting of small hydrophobic amino acids.
- Recognized by Signal Recognition Particle (SRP), which binds the ER signal sequence as protein emerges from the ribosome.
- SRP slows protein synthesis until it binds to an SRP receptor on the ER membrane.
Translocation Channel:
- SRP and receptor function to connect ribosomes with ER translocation channels.
- Signal sequence opens the channel, threading the protein through the membrane as a loop.
- Protein released into ER lumen after signal sequence is cleaved by signal peptidase.
- Signal peptide is degraded; a plug protein may close inactive channels.

Single-Pass Transmembrane Proteins:
- N-terminal signal sequence initiates translocation.
- Stop-transfer sequence halts transfer, embedding protein in the membrane.
Multi-Pass Membrane Proteins:
- Internal signal sequences start transfer; stop-transfer sequences halt and anchor proteins.
- Process resembles a sewing machine, with multiple start/stop sequences stitching the protein into the bilayer.

ER plays a crucial role in protein targeting and integration into cellular membranes.
The process ensures proper orientation and localization of proteins essential for cellular function.