Wednesday, May 29, 2013

The nucleus was the first organelle to be discovered. The probably oldest preserved drawing dates back to the early microscopist Antonie van Leeuwenhoek (1632 – 1723). He observed a "Lumen", the nucleus, in the red blood cells of salmon. Unlike mammalian red blood cells, those of other vertebrates still possess nuclei. The nucleus was also described by Franz Bauer in 1804 and in more detail in 1831 by Scottish botanist Robert Brown in a talk at the Linnean Society of London. Brown was studying orchids microscopically when he observed an opaque area, which he called the areola or nucleus, in the cells of the flower's outer layer. He did not suggest a potential function. In 1838 Matthias Schleiden proposed that the nucleus plays a role in generating cells, thus he introduced the name "Cytoblast" (cell builder). He believed that he had observed new cells assembling around "cytoblasts". Franz Meyen was a strong opponent of this view having already described cells multiplying by division and believing that many cells would have no nuclei. The idea that cells can be generated de novo, by the "cytoblast" or otherwise, contradicted work by Robert Remak (1852) and Rudolf Virchow (1855) who decisively propagated the new paradigm that cells are generated solely by cells ("Omnis cellula e cellula"). The function of the nucleus remained unclear.
Between 1876 and 1878 Oscar Hertwig published several studies on the fertilization of sea urchin eggs, showing that the nucleus of the sperm enters the oocyte and fuses with its nucleus. This was the first time it was suggested that an individual develops from a (single) nucleated cell. This was in contradiction to Ernst Haeckel's theory that the complete phylogeny of a species would be repeated during embryonic development, including generation of the first nucleated cell from a "Monerula", a structureless mass of primordial mucus ("Urschleim"). Therefore, the necessity of the sperm nucleus for fertilization was discussed for quite some time. However, Hertwig confirmed his observation in other animal groups, e.g. amphibians and molluscs. Eduard Strasburger produced the same results for plants (1884). This paved the way to assign the nucleus an important role in heredity. In 1873 August Weismann postulated the equivalence of the maternal and paternal germ cells for heredity. The function of the nucleus as carrier of genetic information became clear only later, after mitosis was discovered and the Mendelian rules were rediscovered at the beginning of the 20th century; the chromosome theory of heredity was developed.

What is nucleus?
In cell biology, the nucleus (pl. nuclei; from Latin nucleus or nuculeus, meaning kernel) is a membrane enclosed organelle found in eukaryotic cells. It contains most of the cell's genetic material, organized as multiple long linear DNAmolecules in complex with a large variety of proteins, such as histones, to form chromosomes. The genes within these chromosomes are the cell's nuclear genome. The function of the nucleus is to maintain the integrity of these genes and to control the activities of the cell by regulating gene expression — the nucleus is therefore the control center of the cell. The main structures making up the nucleus are the nuclear envelope, a double membrane that encloses the entire organelle and separates its contents from the cellular cytoplasm, and the nuclear lamina, a meshwork within the nucleus that adds mechanical support, much like the cytoskeleton supports the cell as a whole. Because the nuclear membrane is impermeable to most molecules, nuclear pores are required to allow movement of molecules across the envelope. These pores cross both of the membranes, providing a channel that allows free movement of small molecules and ions. The movement of larger molecules such as proteins is carefully controlled, and requires active transport regulated by carrier proteins. Nuclear transport is crucial to cell function, as movement through the pores is required for both gene expression and chromosomal maintenance.
Although the interior of the nucleus does not contain any membrane-bound subcompartments, its contents are not uniform, and a number of subnuclear bodies exist, made up of unique proteins, RNA molecules, and particular parts of the chromosomes. The best known of these is the nucleolus, which is mainly involved in the assembly of ribosomes. After being produced in the nucleolus, ribosomes are exported to the cytoplasm where they translate mRNA.

The nucleoskeleton
The nucleoskeletal framework that remains insoluble after treatment of nuclei with non-ionic detergents, followed by nuclease treatment and high salt extraction to remove chromatin and soluble proteins, is generally termed the nuclear matrix. This nucleoskeleton consists of two parts namely, the nuclear lamina and a network of intricately structured fibres connected to the lamina and distributed throughout the nuclear volume. These highly structured fibre assemblies have been shown to be attached to an underlying network of 10 nm core filaments (Nickerson, 2001). The nuclear lamins A, B and C are the major structural components of the peripheral lamina. Additional proteins that connect the lamina to the nuclear envelope and the heterochromatin are clustered at the nuclear periphery. Other nuclear matrix-associated components like hnRNP complexes, newly transcribed full-length mRNA, RNA polymerase I and II, various transcription factors and spliceosomal complexes are positioned on the underlying network of branched 10 nm filaments that is connected to the nuclear lamina (Jackson and Cook, 1988; He et al., 1990; Nickerson et al., 1997). These associations might be dynamic and allow for considerable plasticity in nuclear architecture and function. Furthermore, numerous studies have suggested the presence of an organizing structure such as the nuclear matrix to coordinate the spatial regulation of DNA synthesis (Dijkwel et al., 1979; Berezney and Buchholtz, 1981; Collins and Chu, 1987; Vaughn et al., 1990; Hozak et al., 1993; 1994). The major candidate proteins that are likely to comprise the nucleoskeleton are lamins and nuclear actin. Nuclear pore complexesIn eukaryotic cells, the genetic information is stored in the nucleus and protein synthesis occurs in the cytoplasm. This compartmentalization offers additional regulation of gene expression, at the expense of a large amount of energy, to ensure the bidirectional movement of macromolecules between the two compartments through the nuclear pore complexes (NPCs). For example, different classes of RNA synthesized in the nucleus, including messenger RNA (mRNA), ribosomal RNA (rRNA), small nuclear RNA (snRNA) and transfer RNA (tRNA) have to be exported from the nucleus to the cytoplasm. Similarly, a large number of nuclear proteins and matured small nuclear ribonucleoproteins (snRNPs) are actively imported into the nucleus. The NPC has been shown to have a remarkable structure with a total mass of 124 x 106 daltons (Reichelt et al., 1990). It has a wheel-like array of a spoke ring complex, a central transporter, a cytoplasmic ring and a nuclear octagonal ring that serve as attachment sites for the cytoplasmic filaments and the nuclear basket complex respectively. The components of the spoke ring complex are interconnected to form a lumenal ring that is attached to the nuclear lamina (Yang et al., 1998). Small metabolites and molecules can freely diffuse through the NPC, which provides an aqueous channel of approximately 9 nm in diameter. However, larger macromolecules such as proteins require the presence of a signal sequence rich in basic amino acids called the nuclear localization signal (NLS) for active transport into the nucleus through the NPC. Several receptors for nucleocytoplasmic transport pathways have been identified. These receptors recognize the NLSs of their cargoes and mediate their transport. These receptors fall under a related family of shuttling transport factors called importins and exportins. These factors interact with distinct classes of transport cargoes by recognizing their NLSs, and share the ability to bind to a subset of nuclear pore proteins, also called nucleoporins. The molecular interaction of importins and exportins with their cargoes and the nucleoporins is an energy-dependent process.