The Nuclear Pore Complex

DNA is enclosed by the nuclear envelope consisting of two concentric membranes - outer and inner nuclear membranes which contain numerous protein complexes called the Nuclear Pore Complexes or NPCs.

The outer nuclear membrane is studded with ribosomes which synthesize proteins that are imported into the perinuclear space (the space between outer and inner nuclear membranes).

The Nuclear Envelope is perforated with Nuclear Pore Complexes

It is estimated that there are around 3000-4000 NPCs in a typical mammalian cell weighing about 125 megadaltons.
These complexes are dynamic structures which contain about 50-100 different proteins called nucleoporins arranged in an octagonal symmetry.

Nucleoporins also contain aqueous channels that allow small water-soluble molecules to diffuse through. Large molecules, however, require the help of nucleoporins in order to be transported in and out of the nucleus. While the functional diameter of the NPC is about 9 nm, it has been claimed that the pore can dilate up to 26 nm to allow passage of molecules.


Structure of NPC

The Nuclear Pore Complex

The Nuclear Pore Complex has three basic elements:

• the central core
• the nuclear basket
• cytoplasmic fibrils

It also has four basic structural units:

• column subunits - form the pore wall
• annular subunits - jut out a "spoke-shaped protein" into the pore
• lumenal subunits - function in anchoring the complex to nuclear membrane and
• ring subunits - host fibrils on both nuclear and cytoplasmic faces of the complex

Obviously, the cytoplasmic fibrils extend into the cytoplasm and are known to interact with cargo on the cytoplasmic side.

On the nuclear side, the fibrils converge and form a basket-shaped structure called the nuclear basket.

More information on Nuclear Pore Complexes can be found here.

So how does the cell know what proteins need to be imported into the nucleus?

Nuclear Localization Signals (NLS)

All nuclear proteins carry Nuclear Localization Signals (NLS) which act as "tags" that direct them to the nucleus.

These signals are usually one or two short sequences rich in positively charged amino acids such as lysines and arginines. It has been noted that the precise location of these short sequences within the amino acid sequence in not important so long as they are exposed on the surface of the protein to be recognized by nuclear import receptors (discussed in the next post).

* A distinguishing feature of this mechanism of transport of proteins (ie. through NPCs) from that in other organelles is the fact that since transport occurs across a large aqueous pore, proteins are able to be transported in their intact forms. However, this has been contradicted by several studies that observed that very large cargo (such as mRNA molecules) do in fact undergo some sort of restructuring to be able to pass through.