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Understanding the Ran GTPase Cycle

May 19, 2025

Lecture Notes: The Ran GTPase Cycle and Nuclear Transport

Overview

  • Ran GTPase Cycle is involved in nuclear transport.
  • Proteins like transcription factors are transported from the cytosol into the nucleus.
  • Transport occurs through nuclear pore complexes (NPCs).
  • NPCs are composed of approximately 30 types of proteins called nucleoporins.

Nuclear Membrane

  • Also called the nuclear envelope.
  • It is a double membrane separating the nucleus from the cytosol.

Protein Transport Mechanisms

  1. Passive Diffusion

    • Proteins ≤ 60 kDa can passively diffuse through nuclear pores.
    • Larger proteins require active transport.

  2. Active Transport

    • Facilitated by proteins known as importins and exportins.
    • Importins bind to proteins entering the nucleus via a nuclear localization signal.
    • Exportins bind to proteins exiting the nucleus via a nuclear export signal.

Ran Protein

  • Exists in two forms: Ran GDP (cytosol) and Ran GTP (nucleus).
  • About 95% of Ran protein is located in the nucleus.

Nuclear Import Process

  1. Proteins and importin (α or β) enter the nucleus via NPCs.
  2. RCC1 in the nucleus converts Ran GDP to Ran GTP by adding a phosphate group.
  3. Ran GTP binds to importins, causing them to release their cargo proteins.
  4. Ran GTP-importin complex exits the nucleus back to the cytosol.
  5. Ran GAP and Ran binding proteins hydrolyze Ran GTP to Ran GDP, disassociating importin.

Nuclear Export Process

  1. Exportins bind to cargo proteins in the nucleus via a nuclear export signal.
  2. Exportin-cargo complex binds Ran GTP and exits the nucleus through NPCs.
  3. Ran GAP and Ran BP hydrolyze Ran GTP to Ran GDP, disassociating exportin and cargo.
  4. Exportins and Ran GDP re-enter the nucleus to continue the cycle.

Summary

  • The Ran GTPase cycle is crucial for the import and export of proteins across the nuclear envelope.
  • Importins and exportins play key roles in active transport.
  • The cycle involves the conversion between Ran GDP and Ran GTP facilitated by RCC1 and Ran GAP/BP.

Note: Always remember the role of nuclear pore complexes and the importance of nucleotide signals in guiding proteins.

End of Lecture

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