The cell nucleus is the most noticeable organelle within a eukaryotic cell, and perhaps the most important and defining feature of the eukaryotic cells.
Shape and Appearance
The nucleus is normally around 5-10 μm in diameter in many multicellular organisms, and the largest organelle in the cell. The smallest nuclei are approximately 1 μm in diameter and are found in yeast cells.
Mostly the shape of the nucleus is spherical or oblong. Usually cells have one nucleus but many at times there are multinucleated cells. Multinucleation in cells may be due to karyokinesis (when cell undergoes nuclear division) or when cells fuse to form syncytium, like in mature muscle cells.
The nucleus has very important roles to play. As it contains genetic material, it coordinates cell activities like protein synthesis and cell division. Anatomically the nucleus is made up of several components:
- nuclear envelope
- nuclear lamina
When a cell is histologically stained, the nucleus normally appears as a large, dark organelle, mostly at or near the centre of a cell.
Structure of the Nucleus
As its name suggests, the nuclear envelope surrounds the nucleus, separating it from the cell's cytoplasm. It is a double membrane. Each membrane is a phospholipid bilayer associated with proteins, and the two membranes are divided by 20 to 40 nm of space. The two membranes of the nuclear envelope are often referred to as the inner and outer nuclear membranes. The outer membrane is continuous with the cell’s endoplasmic reticulum, and therefore the space between the inner and outer nuclear membranes links to the lumen of the endoplasmic reticulum. Like the endoplasmic reticulum, the outer nuclear membrane has ribosomes attached to it. Contrastingly, the inner membrane of the nuclear envelope is attached to proteins that are specific to the nucleus, and therefore found nowhere else.
The nuclear envelope is perforated with tiny pores with diameters of around 100 nm. The inner and outer membranes of the envelope are continuous around the pores. Each pore is lined with a structure of 50 to 100 different proteins known as the nuclear pore complex. These pore complexes regulate the movements of macromolecules, RNAs and proteins into and out of the nucleus. This movement of molecules is known as nuclear transport. Small molecules can move passively through the pores, but larger molecules, including RNAs and many proteins, are too large for this and must move actively. During this active process, they are selectively recognised and transported in one specific direction. The traffic of RNAs and proteins through the nuclear pore complex is particularly important, as they play a role in gene expression.
The inner nuclear membrane is internally lined by protein filaments meshwork organised in a net-like fashion, called nuclear lamina. The proteins that make up the nuclear lamina are known as lamins, which are intermediate filament proteins. These support the nuclear envelope, ensuring that the overall shape and structure of the nucleus is maintained.
In addition to lamins there is another set of membrane proteins called lamina associated proteins, which help to mediate the interaction between the lamina and inner nuclear membrane. The nuclear lamina, along with protein fibers called the nuclear matrix, is also thought to aid in the organisation of genetic material, allowing it to function more efficiently.
The DNA of a cell is found within the nucleus. It is organised into units known as chromosomes, each containing a long DNA molecule which is associated with various proteins. The DNA coils around protein complexes called nucleosomes, formed of proteins called histones, making it easier for the chromosome to fit inside the nucleus.
The mass of DNA and proteins inside a chromosome is referred to as chromatin. When a cell is not dividing, it is difficult to see the chromosomes within a cell, even when it is stained. However, when DNA prepares and begins to divide, the chromosomes can be visualised more clearly. During the metaphase of mitosis, the chromosomes become visible as they prepare to divide by aligning with one another. The chromosomes are copied, forming sister chromosomes known a chromatids. Human cell nuclei contain 46 chromosomes, although gamete nuclei contain 23. The whole of the nucleus is not filled by chromatin material, in fact, there are chromatin free regions called interchromosomal domains containing poly RNAs.
When a nucleus is not dividing, a structure called a nucleolus becomes visible. In fact, it is the most prominent structure within the nucleus. Usually there is only a single nucleolus present, but some nuclei have multiple nucleoli. It is a mass of granules and fibers attached to chromatin.
The nucleolus is important because it is the site of ribosomal RNA (rRNA) production. Inside the nucleolus, rRNA molecules are combined with proteins to form ribosomes. The nucleolus is involved in rRNA transcription, pre-rRNA processing and ribosome subunit assembly. The nucleolus is not surrounded by a membrane, but it has a unique density, separating it from the surrounding nucleoplasm, and allowing it to be visualised under a microscope. As well as being involved in ribosomal biogenesis, the nucleolus is thought to have other roles, as it contains a number of proteins unrelated to rRNA and ribosome synthesis. It is thought be play a role in activities such as DNA damage repair, cell cycle regulation and RNA editing.
Nucleoplasm is similar to the cytoplasm of a cell, in that it is semi-liquid, and fills the empty space in the nucleus. It is a form of protoplasm and surrounds the chromosomes and nucleoli inside the nucleus. It also has various proteins and enzymes dissolved within it.
Nuclear bodies can be found in the nucleoplasm, and these include structures such as Cajal bodies, Gemini bodies, and Polycomb bodies. Cajal bodies are between 0.3-1.0 µm in diameter, and can be found in proliferating cells such as embryonic and cancerous cells, as well as in cells which have a high metabolic rate, such as neurons. Sometimes referred to as coiled bodies, Cajal bodies are bound to nucleoli by specialised proteins called coilin proteins. Having these proteins concentrated within Cajal bodies improves the efficiency of nuclear processes such as the modification and assembly of UsnRNPs, which can become spliceosomes.
Adjacent to Cajal bodies, Gemini bodies or “Gems” can be found. These comprise Gemin 2 protein and motor neurons gene product (SMN), which are involved in the assembly and maturation of snRNPs.
Mutations in the genes that code for lamins in the nucleus can lead to a number of rare genetic disorders, normally due to a change in the abundance of lamins in the nuclei. Collectively these diseases are known as laminopathies. These diseases include autosomal dominant Emery-Dreifuss muscular dystrophy, Dunnigan-type familial partial lipodystrophy, as well as developmental and aging disorders.
Additionally, certain blood disorders can lead to abnormalities in the nuclei, meaning that analysis of the shape and structure of nuclei in blood cells can lead to diagnoses. For example, Wilson’s disease leads to an increase in glycogen in the nuclei, whilst acute myeloid leukaemia causes nuclei to become cup-shaped.
Moreover, abnormalities in the nucleoli can lead to some forms of rare hereditary disease, as well as degenerative diseases such as Huntington’s and Alzheimer’s. Several diseases can also result from changes in the nuclear envelope. These include cardiomyopathy and muscular dystrophy.