TIME DIMENSION IN CELL BIOLOGY - A AUTORADIOGRAPHIC SURVEY OF THE DYNAMIC FEATURES OF CELLS, CELL COMPONENTS, AND EXTRACELLULAR-MATRIX

Some 50 years ago, Schoenheimer, Hevesy, and their followers discovered that the substances making up the organs of the body were in a dynamic state. When a precise method was devised for radioautography in 1946, it became possible to examine how whole cells, intracellular components, and extracellular matrix participated in this dynamism. Whole cells have been classified according to their ability to proliferate, as measured in H-3-thymidine radioautographs. Some cell populations, such as cortical neurons, do not proliferate and are called static. Many others, such as kidney cell populations, proliferate at a slow rate that decreases with age and are called expanding. The cells in these two groups appear to live on as long as the individual. In a third group, cell populations such as those of surface epithelia and blood proliferate at a rapid rate and are called renewing; new cells continually arise from mitosis, differentiate to a functional stage and, thereafter, die. Renewing cell populations are under the dual control of genetic and environmental factors. Intracellular components turn over at variable but generally rapid rates. Thus, all cells, whether they belong to static, expanding or renewing populations, are labeled in radioautographs prepared after injection of H-3-amino acids and, therefore, continually synthesize proteins. The newly-synthesized proteins migrate from ribosomes to nucleus, mitochondria and endoplasmic reticulum. From the latter, they may be traced to the Golgi apparatus, where their glycosylation is completed; they are then delivered to lysosomes, plasma membrane and, outside of some cells, by means of secretory granules. Like proteins, other intracellular components, namely RNAs, and lipids undergo turnover. However, while DNA and associated histones may be duplicated for mitosis, they otherwise remain completely stable. Extracellular matrices are of two main types: stromal matrices and basement membranes. Stromal matrices include a series of compact structures, such as dentin, elastic tissue and bone, whose components are mainly stable, with the exception of bone remodeling areas. As for connective tissue components, the turnover rate seems to decrease with the compactness. In basement membrane, limited evidence indicates that laminin turns over at a slow rate and heparan sulfate proteoglycan at a rapid rate, while type IV collagen might be stable. Thus, with few exceptions, extracellular matrix components turn over slowly or not at all. In conclusion, the dynamic state of body components arises from three different sources: (1) the extracellular matrix provides a rather small contribution; (2) cells in renewing populations provide an important share; (3) the turnover of intracellular components, that is proteins, RNAs, and other substances is the major factor in the dynamism of body components. The renewal of intracellular components occurs from bacteria to man. It is an essential feature of life.