Atlas of Plant and Animal Histology
Home / The cell / Nucleus / Nuclear pores

The cell. 4. Nucleus.


Nuclear pore are protein complexes located at the nuclear envelope. They control the molecular trafficking between nucleoplasm and cytoplasm.

Proteins of the nuclear pores are known as nucleoporins.

The transport of molecules through nuclear pores is selective and uses the energy generated by the gradient concentration of ran-GTP and ran-GDP.

Importins and exportins are two families of proteins that recognize molecules that cross nuclear pores. Importins bind proteins that enter the nucleus and exportins molecules that go out the nucleus. Importins and exportins interact with nucleoporins during the trafficking.

The nuclear envelope consists of and outer membrane, an inner membrane, and a perinuclear space between them. At some points, the inner and the outer membranes are fused in a way that form open channels that make possible a direct communication between cytoplasm and nucleoplasm. Nuclear pore complexes are located in these channels of the nuclear envelope. They are very large protein aggregates, so big that can be observed with the electron microscope (see Figure 1). They are the communication gates between nucleoplasm and cytoplasm since all the molecular trafficking between these two compartments occurs through the nuclear pore complexes. Controlling this traffic is vital for the cell. For example, the entering of transcription factors into the nucleus influences the expression of particular genes, and the exit of mRNA makes possible the synthesis of proteins. Thus, nuclear pores are a key element during cell physiology.

Nuclear pore complexes are very abundant in cells showing an intense trafficking between nucleoplasm and cytoplasm, as in differentiating cells. It is estimated around 11 nuclear pore complexes by μm2 of nuclear envelope, which means around 3000 to 4000 nuclear pores in one cell. In the cell cycle, new nuclear pore complexes are synthesized and assembled during interphase, previously to mitosis. However, they are also synthesized after cell division. In open mitosis, where the nuclear envelope gets disorganized, the nuclear pore complexes are also disorganized and the its proteins are free in the cytoplasm. After mitosis, these nuclear pore proteins are grouped again in new nuclear pore complexes while the nuclear envelope is assembled at the same time.

Nuclear pore

Figure 1. Transmission electron microscopy image of the nuclear envelope. The two constrictions of the nuclear envelope are nuclear pore complexes.

Nuclear pore

Figure 2. Protein organization in a nuclear pore complex (modified from Beck et al., 2007)

Proteins of the nuclear pore complexes are known as nucleoporins. In yeasts, 30 different nucleoporins have been found, whereas in metazoa may be more than 40 different nucleoporins. There are several copies of each nucleoporin in the same nuclear pore complex. Thus, in mammals, a nuclear pore complex contains around 500 to 1000 nucleoporins. The total structure is 100 to 150 nm wide, 50 to 70 nm high, and contains an inner hydrophilic passage of around 40 nm. Nuclear pore complexes are among the largest protein structures of the cell, about 125000 kDa. It is remarkable that nucleoporins show a great stability, sometimes as long as the whole life of the cell, whereas the lifetime of a common protein may last a few days.

Nucleoporins are grouped in 8 blocks, which are organized as a regular octagon forming ring-like structures (Figure 2). The cytoplasmic ring faces the cytoplasm, the radial ring is in the channel of the nuclear envelope and anchors the nuclear pore complex to the nuclear envelope, and the nuclear ring is facing the nucleoplasm. Furthermore, there are fibrils extending from each of the 8 blocks: cytoplasmic fibrils and intranuclear fibrils. The intranuclear fibrils are connected to the nuclear ring by one of their ends and to other proteins that form another intranuclear ring known as distal ring. Intranuclear fibrils and distal ring form the nuclear basket, also known as nuclear cage.

Besides the structural role, nucleoporins are classified according to their function. There are transmembrane proteins for anchoring the whole complex to the membrane of the nuclear envelope. The scaffold proteins form the rings, and inner proteins that form the hydrophilic passage and regulate the molecular trafficking through the nuclear pore complex. Those proteins that form the fibrils and nuclear cage recognizespan> the molecules, and are therefore allowed to cross the nuclear passage. I should be noticed that molecules coming in and going out of the nucleus do no need to cross any membrane, but just the hydrophilic channel.

Nuclear pore complex contains an hydrophilic passage of about 80 to 90 nm in diameter. When nuclear pore complex is at rest (no trafficking) the usable space is about 45 to 50 nm in diameter, and it can be increased when some molecule is being transported. Small molecules (less than 60 kDa) like salts, nucleotides, small molecules and short polypeptides can cross freely through the hydrophilic channel, but other larger molecules with physiological roles are not allowed to across freely. Even some molecules smaller than 20-30 kDa such as histones, tRNAs and small mRNAs may need the involvement of the nucleoporins to cross the nuclear envelope. The selective transport, mediated by nucleoporins, is known as passive facilitated transport. Energy is not needed for it. The nuclear pore complex does not determine the direction of the transport, getting in or out the nucleus, but molecules travels according to a gradient of the Ran proteins (Figure 3). The energy is spent in generating this Ran gradient.

Ran Gradient

Figure 3. Ran gradient between the cytoplasm and nucleoplasm. In the cytoplasm, the energy needed to create this gradient is supplied by ATP, transforming Ran-GDP in Ran-GTP. Thus, the nucleoplasm is a sink of Ran-GDP and a source of Ran-GTP. In the cytoplasm, Ran-GTP is converted in Ran-GDP. Thus, the cytoplasm is a source of Ran-GDP and a sink of Ran-GTP. In this way two gradients are created, Ran-GDP and Ran-GTP. The size of the icons in the figure depicts levels of concentration.

Trafficking through a nuclear pore complex is high, with more than 1000 translocations per second. This movement of molecules across the nuclear envelope is regulated by the gradient of Ran proteins. Ran are involved in both importing and exporting molecules between the nucleus and the cytoplasm. They generate the Ran-GTP/Ran-GDP needed for the transport, and it is the generation to these gradients that consumes ATP. Ran molecules can be in three states: Ran-GTP, Ran-GDP and Ran. The state of a Ran molecule depends on several enzymes. In the nucleoplasm, Ran-GDP is more abundant, whereas Ran-GTP is concentrated in the cytoplasm (Figure 3).

Caryopherins are a family of proteins, divided in two subfamilies: importins and exportins, responsible for selecting the molecules that can cross the nuclear pore complex. Proteins that need to be imported into the nucleus have a particular amino acid sequence, known as entrance signal peptide, and those that need to be exported to the cytoplasm have an exit signal peptide. These short peptide sequences are not identical for all proteins, but similar. The entrance and exit signal peptides are recognized by importins and exportins, respectively. There are members of importins and exportins with different affinity for the import and exit sequences. Nucleoporins do not interact directly with the transported molecules, but with importins and exportins.

Importin and exportin use the Ran-GTP/Ran-GDP gradients for transporting the cargoes in a specific direction. In this way, importins spontaneously joins to their cargoes in the cytosol, but once in the nucleoplasm cargoes are released by Ran-GTP, which is abundant inside the nucleus. On the other hand, exportins need Ran-GTP to join to their cargoes in the nucleosplasm, but once they (exportin-cargo-Ran-GTP) are translocated to the cytoplasm, Ran-GTP is converted in Ran-GDP that breaks the complex, and exportin, cargo and Ran-GDP are detached from each other and are free in the cytosol.

Molecules to be specifically transported across the nuclear envelope need to have export or import sequences, but it is no enough. These sequences need to be accessible to exportins and importins. Conformational changes or chemical modifications of the molecules having these sequences may prevent karyopherins recognizing them, so they remain in the nucleoplasm or cytoplasm until the sequence is exposed. This mechanism adds a new layer of regulation to nucleus-cytoplasm trafficking.

Once in the other site, importins and exportins will release their cargoes. Cargoes are proteins, but RNAs must also be exported. Different RNAs use different transport mechanisms. For example, tRNA joins to exportin-t which uses the Ran-GTP gradient. rRNA transport is no well known yet. mRNA, however, does not always use the Ran-GTP mechanism but the Tap/Nxt protein gradient, which interacts with nucleoporins and consume ATP as well. Some types of mRNA use Crm1 proteins, that relies on the Ran proteins.

At transmission electron microscopy, heterochromatin is usually observed close to the nuclear envelope, but not near to nuclear pores. Therefore, it is thought that the chromatin near to nuclear pores is a site where expression of inducible genes is facilitated. This is reasonable since nuclear pores are the gate for mRNA to get out. This less condensed chromatin appears to be the result of the direct interaction between nucleoporins and chromatin.


Beck M, Lucic V, Forster F, Baumeister W, Medalia O . Snapshots of nuclear pore complexes in action captured by cryo-electron tomography. 2007. Nature 449:611-615.

Carmody SR, Wente SR . mRNA nuclear export at a glance. 2009. Journal of cell science 122:1933-1937.

Guo T, Fang Y. . Functional organization and dynamics of the cell nucleus. 2014. Frontiers in plant biology. vol 5. Artículo 378. doi: 10.3389/fpls.2014.00378 Read the article.

Nuclear envelope Chromatin

Home / The cell / Nucleus / Nuclear pores
Updated: 2018-07-22. 09:03