Nuclear Cytoplasmic Transport

What are nuclear pore complexes (NPCs)?

NPCs act as gateways between the nucleus and the cytoplasm.

What are FG nups?

FG nups are domains rich in phenylalanine and glycine.

What are nuclear localization signals (NLSs)?

An NLS is a signal that allows the import or export of a protein through the NPC.

What is required for nuclear import?

1. NLS containing cargo protein

2. Nuclear import receptors

3. Ran

4. Ran-GAP

5. Ran-GEF

6. NTF2

7. CAS

Summarize the nuclear import process.

1. Nuclear import receptors associate with cargo and bring it to nuclear pore

2. Import receptors interact with FG nups and NPCs to move cargo through pore

3. RanGTP displaces cargo from receptor once in the nucleus

4. Receptors return to cytosol, where Ran-GAP and RanBP1 hydrolyze RanGTP

5. RanGDP dissociates from receptor

What is required for nuclear export?

1. NES containing cargo proteins

2. Nuclear export receptors

3. Ran

4. Ran-GAP

5. Ran-GEF

6. NTF2

Briefly summarize nuclear export.

CRM1 binds to NES-cargo complex in the presence of Ran-GTP. Once outside the cell, RanBP1 and RanGAP disassemble complex in the cytoplasm.

What is the importance of the RanGTP gradient?

Importins only bind in the absence of RanGTP, while exportins only bind in the presence of RanGTP.

How is the RanGTP gradient maintained?

NTF2 transports RanGDP back into the nucleus after export, where RanGEF phosphorylates it into RanGTP.

What diseases can dysregulation of nuclear transport machinery lead to?

Cancer, neurodegenerative disease, and inflammation