The cell. 4. Nucleus.
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Nuclear pores are molecular 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 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 and exportins to molecules that go out. These proteins interact with nucleoporins during the crossing.
Nuclear pores are inserted in channels of the nuclear envelope. Although some proteins of the nuclear pores are transmembrane proteins, most of the nuclear pores molecules are associated with the nuclear envelope membranes. Nuclear pores, also known as nuclear pore complexes, are large molecular associations, visible by electron microscopy. They are the communication gates between nucleoplasm and cytoplasm, since all the molecular trafficking between these two compartments occurs through nuclear pores. The control of this traffic is vital for the cell. For example, the entering of transcription factors into the nucleus influences the expression of particular genes. Thus, nuclear pores are a key element during cell differentiation, but also during normal cell physiology.
Nuclear pores are very abundant in cells showing a high traffic between nucleoplasm and cytoplasm, as happen in differentiating cells. It is estimated around 11 nuclear pores by µm2, which means around 3000 to 4000 nuclear pores in one cell.
Protein organization in a nuclear pore (modified from Beck et al., 2007)
Proteins of the nuclear pores are known as nucleoporins. 30 different nucleoporins have been found in the nuclear pore of yeasts, whereas in metazoa may be more than 40 different nucleoporins. In mammals, a nuclear pore contains around 400 nucleoporins, many of them are repeated. Nucleoporins are grouped in 8 blocks, which are organized as a regular octagon showing rings. 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 proteins of the distal ring. Intranuclear fibrils and distal ring form the nuclear basket, also known as nuclear cage.
Transmission electron microscopy image of the nuclear envelope. The two constrictions of the nuclear envelope are nuclear pores.
Nuclear pore contains a hydrophilic passage of about 80 to 90 nm in diameter. When nuclear pore is at rest (without trafficking) the usable space is about 45 to 50 nm in diameter, but it can be increased when transport occurs. Small molecules (less than 20-30 kDa) can cross freely through the hydrophilic channel of the nuclear pore, but other larger molecules with physiological roles are not allowed to across freely. But even some small molecules such as tRNAs or small mRNAs may need the participation of nucleoporins to cross toward the cytoplasm. If nucleoporins do not take part, the transport is known as passive diffusion movement, but if nucleoporins are at work, then we have passive facilitated transport. Although it is passive transport, molecules are traveling against gradient concentration and then they need the energy supplied by other gradients: the Ran-GTP /Ran-GDP molecules. Let's see how it happens (see figure).
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.
Ran-GTPases regulate the nuclear pore trafficking. Ran-GTPases are involved in both import and export of molecules between the nucleus and cytoplasm, by creating the Ran-GTP/Ran-GDP gradients needed for this transport, and it is in the creation to these gradients where energy is consumed. 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 (see figure on the left)
Proteins that need to be imported into the nucleus have an 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 sequences of amino acids are recognized by importins and exportins, respectively. Nucleoporins do not interact directly with the transported molecules but with importins and exportins. The importin-transported molecule and exportin-transported molecule complexes use either Ran-GTP or Ran-GDP gradients, in order cross the nuclear pore. 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 ☆
|« Nuclear envelope||Chromatin »|
Updated: 2016-05-09. 13:43
Atlas of Plant and Animal Histology
Dep. of Functional Biology and Health Sciences.
Faculty of Biology.
University of Vigo