The cell nucleus houses the genetic blueprint, DNA, and is enclosed by a protective double membrane known as the nuclear envelope. This envelope is not an impenetrable barrier; instead, it is perforated by gateways called nuclear pore complexes (NPCs). These structures are intricate molecular machines that control all traffic moving between the nucleus and the surrounding cytoplasm. This regulated transport is fundamental to cellular life, ensuring that proteins for DNA replication get in, and messenger RNA carrying genetic instructions gets out. The constant, controlled exchange of molecules is foundational for processes from gene expression to cell division, and any NPC dysfunction can be linked to a variety of diseases.
The Grand Design: Overall Architecture of the NPC
The nuclear pore complex is one of the largest protein assemblies in a cell, embedded within the nuclear envelope where the inner and outer nuclear membranes fuse. In vertebrates, a single NPC has a molecular mass of approximately 124 megadaltons and is constructed from hundreds of individual protein molecules. Its overall diameter measures around 120 nanometers, with a central transport channel that varies in width from about 5.2 nanometers in humans to 10.7 nanometers in certain frogs. A vertebrate cell nucleus may contain thousands of these pores, with the number fluctuating based on the cell’s metabolic activity.
A defining feature of the NPC’s architecture is its eightfold rotational symmetry around a central axis, creating a wheel-like appearance. This octagonal structure is a conserved feature across nearly all eukaryotic life, from yeast to humans. This design forms a stable yet dynamic gateway that can transport up to 1,000 molecules per second.
The Protein Bricks: Nucleoporins (Nups)
The nuclear pore complex is constructed from a set of approximately 30 different proteins known as nucleoporins, or Nups. Multiple copies of these Nups come together to form the entire structure, with around 1,000 individual protein molecules in a single human NPC. These protein components can be grouped into categories based on their position and function.
One major group consists of transmembrane Nups, which are responsible for anchoring the entire NPC assembly into the nuclear envelope. They are embedded within the double membrane, ensuring the pore remains fixed.
Another category is the scaffold Nups, which form the structural core of the NPC and the ring-like structures that provide its foundational shape. A third class of nucleoporins are the channel Nups, which line the interior of the central transport channel and are responsible for the NPC’s selective permeability.
Assembling the Megastructure: Key Subcomplexes
The individual nucleoporins assemble into larger, stable modules that act as the primary building blocks of the NPC. The main body is a core scaffold composed of three interconnected rings: a cytoplasmic ring facing the cytoplasm, a nuclear ring facing the nucleus, and an inner ring complex sandwiched between them.
Extending from the cytoplasmic ring are flexible protein strands called cytoplasmic filaments, which act as a primary docking site for molecules destined for nuclear import. On the opposite side, a structure known as the nuclear basket extends from the nuclear ring and plays a role in the export of messenger RNA.
Connecting these outer rings is the inner ring complex, which anchors the channel Nups whose FG-repeats fill the central passageway. This channel is not an open tube but is densely packed with these disordered protein regions, creating a selective gate. This meshwork allows small particles to diffuse through freely while requiring larger molecules to have the proper credentials to pass.
Dynamic Structure: Assembly and Disassembly
The nuclear pore complex is a dynamic structure that undergoes assembly and disassembly throughout the cell cycle. New NPCs can be assembled into an intact nuclear envelope during interphase, the period of cell growth. This process allows a cell to increase the number of pores as its metabolic needs for transport grow, with pre-formed subcomplexes of Nups being inserted into the nuclear envelope.
In higher eukaryotes, a more dramatic process occurs during mitosis. As the cell prepares to divide, the entire nuclear envelope, including all its embedded NPCs, breaks down. The NPCs disassemble into smaller, soluble subcomplexes, which are then distributed throughout the dividing cell. Once division is complete and two new daughter cells are formed, the nuclear envelope reforms around the segregated chromosomes. During this reformation, the NPC subcomplexes are recycled and reassembled to build new pores in the nascent nuclear envelopes of the daughter cells.