Endocytosis macromolecule degradation

Endocytosis for degradation of macromolecules and uptake of nutrients involves phagocytosis, pinocytosis and autophagy 151 The constitutive pathway is also known as the default pathway because it does not require any type of signal to enter 154... 

Most pathways in the endocytic system are shared with cells in general, but a special case exists in synaptic vesicle cycling, which is unique to neurons and a keystone in neuronal function. Three categories will be considered here endocytic processes important for degradation of macromolecules and uptake of nutrients constitutive and regulated neuroendocrine secretion and receptor-mediated endocytosis. Synaptic vesicle cycling will then be considered separately and in greater detail. 

Lysosomes in animal cells are bounded by a single membrane. They have an acidic internal pH (pH 4-5), maintained by proteins in the membrane that pump in H+ ions. Within the lysosomes are acid hydrolases enzymes involved in the degradation of macromolecules, including those internalized by endocytosis. 

Lysosomes are in effect a cellular waste-bin, and play an important role in the turnover and degradation of cytoplasmic organelles and phago-cytosed particles. They facilitate receptor-mediated endocytosis of many macromolecules from the cell membrane. Lysosomes carry hydrolases that degrade nucleotides, proteins, lipids and phospholipids they also remove carbohydrate, sulphate, or phosphate groups from molecules. Lysosomes store iron, either as soluble ferritin or as products of ferritin degradation, such as haemosiderin. Abnormalities associated with lysosomal function cause a variety of storage disorders such as Tay-Sachs disease [9]. 

Several systems have been identified in cells to mediate protein turnover through degradation. Lysosomes contain a number of proteases and other hydrolytic enzymes (Fig. 27.5). All of these enzymes are acid hydrolases and have an optimum activity at -pH 5. A primary role of lysosomes is to degrade proteins and other macromolecules that have been imported into the cell by endocytosis. Endocytosis is the process by which receptors on the cell surface... 

Pearse and Bretscher (1981) have discussed the role of coated vesicles in membrane synthesis and function. Eukaryotic cells are able to specifically take up macromolecules by absorptive endocytosis. The macromolecules are usually transferred to lyso-somes where they may be degraded. The first stage of the process involves the binding of macromolecules to receptors which are localized in coated pits. The latter are indented sites on the plasma membrane and the coated pit buds into the cytoplasm to form a coated vesicle in which lie the endocytosed macromolecules. The coated vesicle sheds its coat rapidly and the endocytic vesicles fuse with each other. This allows receptors to be returned to the plasma membrane while the contents are transferred to the lyso-somes. In order to explain how lysosomal and plasma membranes remain different, it was suggested that the coated pits are able to accept certain macromolecules while excluding others. The accepted proteins enter the coated pit and were presumed to bind directly or indirectly to clathrin. Clathrin, a 180000-dalton protein on the cytoplasmic face of coated pits, provides the polyhedron skeleton for the coated vesicles. Examples of the use of coated vesicles for mediated endocytosis are in the uptake of low-density lipoprotein from the blood and in humans for the transport of immunoglobulins from the mother to the child. For other mammals such as the rat the antibodies are selectively absorbed from the mother s milk by the intestinal epithelium. Coated vesicles also provide a mechanism for virus transport into cells. 

---