Cell growth and division occur in an orderly, highly regulated, progressive series of events called the cell cycle. Advancement of cells through the cell cycle is driven by a small family of intracellular proteins, principal of which are the cyclins and a 34,000-molecular-weight protein, kinase. The cell cycle culminates in mitosis, a process that results in the production of two genetically identical diploid daughter cells. The chromosome separation events of mitosis occur as a result of the workings of the mitotic spindle apparatus, while the process of cytoplasmic division, or cytokinesis, is directed by the contractile ring. Unlike mitosis, meiosis produces nonidentical haploid cells. Meiosis, which occurs only in gonadal tissues, results in the production of oocytes. By the process of fertilization, a new diploid is produced. Progression of cells through the cell cycle in multicellular organisms also can be affected by cell-cell interactions. This occurs when one cell secretes a growth factor that either stimulates or suppresses cell division in neighboring cells. Although cellular proliferation is tightly regulated in multicellular organisms, cells occasionally escape from these regulatory controls with resulting formation of cancerous tumors. Molecular analyses of the DNA in tumor cells have resulted in the identification of the mutated genes that allow for the onset of a cancer. The protein products of these genes, called proto-oncogenes and tumor suppressor genes, appear to play key roles in the regulation of cell growth in humans.
Tissues are formed by the interactions of cells with other cells and the extracellular matrix. Cell-cell interactions can occur either by adherence of neighboring cells at distinct organized regions called junctions or by the binding of randomly scattered cell surface molecules to surface molecules on adjacent cells. Cell junctions can be classified according to function, with the integrity of most types of junctional complexes being dependent upon the presence of extracellular Ca2+. Tight junctions form at the apical surfaces of cells and inhibit the leakage of ions and molecules from one side of an epithelial sheet to the other side, while gap junctions play a crucial role in cell-cell communication. The anchoring junctions share a common molecular organization that allows for the cytoskeleton of one cell to be attached to the cytoskeleton of neighboring cells. This provides tissues, particularly epithelia, with great strength. The desmosome, a type of anchoring junction that acts like a spot weld to hold cells together, interacts with intermediate filaments, while adherens junctions, which are anchoring junctions that allow for cell adhesion and cellular locomotion, utilize microfilaments. The extracellular matrix also is important for tissue formation. Glycosaminoglycans and proteoglycans form a hydrated gel that is the ground substance of the extracellular matrix. The ground substance is embedded with structural proteins such as collagen, which provides tensile strength to the extracellular matrix, and elastin, which is responsible for the resilient nature of the extracellular matrix. The molecules of the extracellular matrix are attached to one another and to the cells that are embedded in the matrix by interactions with adhesive glycoproteins. Adhesive glycoproteins, such as fibronectin, are the glue that holds connective tissues together. A specialized form of extracellular matrix called the basal lamina underlies all epithelia.
To coordinate cellular activities in multicellular organisms, complex mechanisms of cell-cell communication needed to evolve. A variety of different types of signaling molecules are used by cells, and several different signaling pathways are utilized. In neuronal transmission, electrical signals are converted to chemical signals at synapses. The target cells, either other neurons or muscle cells, then convert the chemical signal back to an electrical signal and respond in an appropriate manner. Cells also can signal target cells at great distances by secreting signaling molecules, or hormones, directly into the bloodstream. Steroid hormones are lipid-soluble molecules that cross the plasma membrane and bind to intracellular receptors. The activated steroid hormone receptors then bind specifically to DNA sequences and directly regulate the transcription of adjacent gene sequences. Most hormones that are secreted by endocrine cells are water-soluble molecules that bind to specific receptors located on the surface of the target cells. The activated receptors are transmembrane proteins that are able to relay the extracellular signal across the plasma membrane to the cytoplasm. This is achieved by the cytoplasmic domain of the activated receptor molecule, which binds to and either activates or represses the activity of a cytoplasmic G-protein. Specific G-proteins then interact with target enzymes located on the inner surface of the plasma membrane to regulate the activity of these proteins. One of these enzymes, adenylate cyclase, is responsible for converting ATP to complementary adenosine monophosphate (cAMP). cAMP then sets off a reaction cascade inside cells by allosterically regulating certain molecules, thereby completing the signal transduction pathway. A second enzyme on the cell surface that is activated by G-proteins is phospholipase C. Phospholipase C cleaves a membrane lipid, phosphatidyl inositol 4,5-bisphosphate (PIP2), into inositol 1,4,5-trisphosphate (IP3) and diacylglycerol. IP3 triggers the release of Ca2+ ions from intracellular storage sites, and the Ca2+ ions then bind to and activate calcium-binding proteins such as calmodulin. Diacylglycerol, however, activates protein kinase C, completing the signal transduction pathway in the cell.
The ability of eukaryotic cells to move through a substrate requires cytoskeletal proteins, which generate propulsion, and constant remodeling of the membrane by endocytosis and exocytosis. The stages in cell movement are the polarization of the cell and identification of a leading edge, extension of a lamellipodium or ruffled edge in the direction of movement, and breakdown of attachment with the extracellular matrix. Sometimes a cell moves toward or away from a particular chemical signal (chemotaxis). This occurs because the chemical binds to receptors on the surface of the motile cell, increasing intracellular Ca2+ at the leading edge. The role of Ca2+ in creating a motoring force is not clear, but it may act through Ca2+-dependent severing proteins to cleave actin filaments both within the leading-edge membrane skeleton and in the cell cortex. The result would be a solation of the cytoplasm in the direction of motion, a membrane capable of being extended by exocytosis and a stabilization of the extension by the rapid polymerization of actin in a direction parallel to the leading-edge lamellipodium. The migratory cell is then steered as a result of the microtubule organizing center and Golgi apparatus being realigned along an axis between the nucleus and leading edge. The Golgi apparatus produces the secretory vesicles, which fuse with the leading edge of the plasma membrane, and these vesicles are transported to the leading edge by microtubule-based translocation. Membrane from the old leading edge then ruffles back toward the trailing end of the cell. During the process of cell migration, the motile cell must make and break interactions with the extracellular matrix in a traction-producing process.
The biochemical and phenotypical properties of a cell are defined by the proteins expressed within the cell. The expression of a protein involves a complex pathway that transfers information from the DNA within the nucleus to the protein-synthetic machinery within the cytoplasm. The first step of this pathway is the synthesis of an RNA molecule from the DNA template by the process known as transcription. All cells in an organism contain a complete complement of genetic material; however, only a selected portion is synthesized into RNA. Thus, the transcription process is highly regulated within each cell. In eukaryotes, RNAs are synthesized from units referred to as genes, which contain the information needed to specify a protein sequence stored in three-nucleotide "words" called codons. The informational content of a gene is not necessarily contiguous in that some noncoding DNA may be found interrupting the sequences that form the functional RNA found in the cell's cytoplasm. These noninformational segments are transcribed and removed from the primary transcript in the nucleus, with the informational or exon segments of the RNA joined together by a process called splicing. Once the functional RNA is formed, it is transported to the cytoplasm via the nuclear pores. Upon exiting the nucleus, a mature RNA can be translated into a polypeptide sequence. The amount of protein that is made from an RNA can be regulated by the level of RNA available to the translational machinery or by the ability of the machinery to select specific RNAs for translation. Some proteins are not able to perform their function upon translation and are subjected to modification following translation. In summary, the transfer of information from DNA to a protein capable of performing a function within the cell involves several steps, each of which is subject to regulation. It is the composite of all the individual steps that determines the final level of expression of any given gene product.