Lecture Notes: Nuclear Transport

Introduction

• Nuclear Transport: Mechanism involving the transportation of molecules between the cytosol and nucleus of the cell.
  • Involves both entry and exit of molecules.
  • Mediated by Nuclear Pore Complexes (NPCs).

Nuclear Pore Complexes (NPCs)

• NPCs: Protein complexes facilitating micro molecule transport.
  • Molecules >5,000 Daltons pass through NPCs.
  • Molecules <5,000 Daltons can pass through passively without energy.

Transport Proteins

• Caryopherins: Transport proteins mediating the process.
  • Two types:
    • Importins: Import proteins or micromolecules into the nucleus.
    • Exportins: Transport proteins from the nucleus to the cytosol.

Signals and Binding

• Importins bind to Nuclear Localization Signal (NLS):
  • Amino acid sequence, usually positively charged (lysines, arginines).
  • Tags proteins for transport.
• Exportins bind to Nuclear Export Signal (NES):
  • Amino acid sequence, hydrophobic (leucines).

Energy Source

• Ran Gradient: Provides energy for the process.
  • Ran protein within the cell facilitates energy provision.

Detailed Process

• Nuclear Membrane/Envelope:
  • Contains Nuclear Pore Complexes.
• Cytosol & Cargo:
  • Protein molecule (cargo) is transported into nucleus via importin.
  • Importin comprises Alpha and Beta domains.
    • Alpha Domain: Binds to NLS.
    • Beta Domain: Carries cargo into nucleus.

Import Process

1. Complex Formation: Importin binds with cargo and NLS, assisted by Ran GDP.
2. Nucleus Entry: Complex enters nucleus.
3. Cargo Release: Importin releases cargo in nucleus.
4. Energy Exchange: Interaction with Ran GEF (Guanine nucleotide exchange factor) swaps GDP for GTP.
5. Return to Cytosol: Importin-NLS-GTP complex exits nucleus.
6. Hydrolysis: Ran GAP (GTPase activating protein) converts GTP back to GDP in cytosol.
7. Cycle Repetition: Returns to initial state.

Export Process

• Similar to import but in reverse direction using NES.

Conclusion

• Overview of nuclear transport mechanisms.
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