Nuclear pore complex and its functions.

Structure of the Nuclear Pore Complex

The NPC is a remarkably conserved structure, approximately 50-100 nm in diameter, composed of around 30 different proteins called nucleoporins (Nups). These Nups assemble into multiple copies to form the complex. The NPC exhibits octagonal symmetry and can be broadly divided into several key structural components:

• Outer Ring: Formed by Y-complex Nups, providing the initial attachment point to the nuclear envelope.
• Inner Ring: Composed of Nup153, it faces the nucleoplasm and plays a role in anchoring the complex.
• Central Transporter: This is the core of the NPC, containing a central channel approximately 40 nm in diameter. It’s lined with FG-Nups.
• FG-Nups: These Nups contain numerous phenylalanine-glycine (FG) repeats, creating a hydrophobic meshwork that acts as a selective barrier.
• Nuclear Basket: Located on the nucleoplasmic side, it’s involved in mRNA export.
• Cytoplasmic Filaments: Extending into the cytoplasm, they interact with the cytoskeleton and transport machinery.

The structure isn't static; it undergoes dynamic changes during transport, opening and closing to allow passage of molecules.

Functions of the Nuclear Pore Complex

1. Bi-directional Transport

The primary function of the NPC is to regulate the transport of molecules between the nucleus and cytoplasm. This transport is bidirectional and highly selective:

• Import: Proteins synthesized in the cytoplasm that are required for nuclear functions (e.g., histones, transcription factors, ribosomal proteins) are imported into the nucleus. This process requires a nuclear localization signal (NLS) on the protein and the importin proteins.
• Export: RNA molecules (mRNA, tRNA, rRNA) and proteins synthesized in the nucleus (e.g., ribosomes) are exported to the cytoplasm. This process requires a nuclear export signal (NES) on the cargo and the exportin proteins.

The transport is driven by the Ran-GTP gradient, established by the Ran-GTPase cycle. Ran-GTP is highly concentrated in the nucleus and low in the cytoplasm, facilitating directional transport.

2. Quality Control

The NPC isn't just a passive gate; it also participates in quality control. It ensures that only properly folded and assembled proteins are transported. Misfolded proteins are retained in the nucleus or exported for degradation.

3. Gene Expression Regulation

The NPC plays a role in regulating gene expression by controlling the access of transcription factors and other regulatory proteins to the nucleus. It also influences mRNA processing and export, impacting the levels of protein synthesis.

4. Signaling Platform

Recent research suggests that the NPC serves as a signaling platform, interacting with various signaling pathways and influencing cellular processes like cell cycle progression and stress response.

5. mRNA Surveillance

The NPC participates in mRNA surveillance mechanisms, identifying and retaining aberrant or non-functional mRNA molecules within the nucleus for degradation, preventing the production of faulty proteins.

Mechanisms of Transport

Transport through the NPC occurs via two main mechanisms:

• Passive Diffusion: Small molecules (<40 kDa) can diffuse passively through the central channel.
• Active Transport: Larger molecules require the assistance of transport receptors (importins and exportins) and the Ran-GTP gradient.

The FG-Nups act as a selective barrier, allowing transport receptors to bind and move through the complex while excluding other molecules. The Ran-GTP gradient provides the energy for directional transport.

Transport Type	Cargo	Signal	Receptor	Ran-GTP
Import	Proteins	NLS	Importin	Promotes Dissociation
Export	RNA/Proteins	NES	Exportin	Promotes Dissociation