Cell Clips Lecture: Protein Transport into the Endoplasmic Reticulum (ER)

Introduction

• Overview: Focus on how proteins are transported into the ER.
• Context: Proteins synthesized in the cytoplasm may remain there or be transported to other cell locations, including the ER, mitochondria, and nucleus.
• Importance of ER:
  • Proteins destined for locations like the cell membrane, endosomes, lysosomes, or outside the cell pass through the ER.
  • In the ER, proteins are modified, folded, and packaged into vesicles to fuse with the Golgi apparatus.

Modes of Protein Transport into the ER

1. Post-Translational Translocation

   • Proteins synthesized by free ribosomes in the cytoplasm.
   • Bound by chaperones that prevent folding and imported via Sec61 translocon.
   • ER Signal Sequence: Recognized by Sec61; hydrophobic region flanked by hydrophilic regions.
   • Mechanism: Protein extends into ER lumen, bound by Bip to prevent backsliding, using a ratchet mechanism.
   • Energy Use: ATP hydrolysis required to release BiP-protein bond.

2. Co-Translational Translocation

   • Process: Proteins enter ER as they are synthesized.
   • Ribosomes on ER Surface: Synthesize proteins directly into Sec61 channel.
   • Signal Sequence: Similar to post-translational but usually at the N-terminus; cleaved by signal peptidase.
   • Signal Recognition Particle (SRP):
     • Binds signal sequence as translated.
     • Stops translation and directs ribosome to SRP receptor at ER membrane.
     • Sec61 binds signal sequence, SRP dissociates, translation continues into ER.

Transmembrane Domain Insertion

• Sec61 Functionality: Opens to insert proteins into ER membrane during translocation.
• Transmembrane Domains:
  • Hydrophobic regions (~20-25 amino acids).
  • Proteins maintain orientation across ER and Golgi.
• Orientation Determinants:
  • Based on charge:
    • +ve amino acids -> cytosol
    • -ve amino acids -> ER lumen.
• Analogy: Similar to sewing with a needle and thread.

Summary

• Two Transport Methods: Co-translational and post-translational.
• Common Features: Both utilize Sec61 and specific signal sequences.
• Key Processes:
  • Post-translational uses chaperones and a ratchet system.
  • Co-translational involves SRP, halts translation, and directs to ER.

Next Steps

• Proteins are further modified and transported to their final destination in subsequent processes.

Note: Watch other Cell Clips videos for details on protein modification and transport in the Golgi apparatus.