Cell Biology, Protein Processing, and Cell Signaling

In order to perform their multiple functions, eukaryotic cells have evolved an internal structural organization that consists of several organelles and an intricate network of protein filaments, called the cytoskeleton, which determines cell shape and regulates its dynamic changes. Organelles are membrane-bound compartments that play fundamental functions in cellular physiology. The nucleus hosts the DNA and is the site where the genetic information is transcribed into RNA molecules that are processed, transported to the cytoplasm and translated into proteins, the final executers of the genetic program of a cell. The mitochondria are numerous in a cell and responsible of the production of most of the ATP molecules derived from the catabolism of organic compounds but are also involved in Ca++ signalling and cell death pathways. Lysosomes and peroxisomes play specialized functions in the digestion of macromolecules and oxidative and detoxifying reactions. The endoplasmic reticulum (ER) is the site for the synthesis of lipids and proteins destined to be part of the cell membranes or secreted into the extracellular space. Proteins exit the ER and enter the Golgi apparatus that is a central sorting and processing station where proteins are packaged into vesicles for transport to their final destination. Due to the complexity of such an internal organization, the elucidation of the molecular mechanisms regulating the synthesis, processing and transport of proteins to the various intracellular compartments has fascinated cell biologists for years. Studies on protein secretion have taken advantage of the powerful genetic approaches applied to yeast, a lower eukaryote. A striking evolutionary conservation in the basic components of protein trafficking and processing was found between yeast and mammalian cells. This chapter will summarize the basic principles of mammalian protein synthesis and processing with a focus on the secretory pathway. Many human proteins that circulate in the blood are secreted and extensively modified by specialized cells and play important functions in human physiology. The findings of many years of research provide the basis for our understanding of the molecular mechanisms of cell biology and how malfunctioning of these processes contributes to human diseases including some haematological disorders.