Lysosomes are specialized for the intracellular digestion of macromolecules. They contain unique membrane proteins and a wide variety of soluble hydrolytic enzymes that operate best at pH 5, which is the internal pH of lysosomes. An ATP-driven H+ pump in the lysosomal membrane maintains this low pH. Newly synthesized lysosomal proteins transported from the lumen of the ER, through the Golgi apparatus; they are then carried from the trans Golgi network to endosomes by means of clathrin-coated transport vesicles, before moving on to lysosomes.
The lysosomal hydrolases contain N-linked oligosaccharides that are covalently modified in a unique way in the cis Golgi so that their mannoses are phosphorylated. These mannose 6-phosphate (M6P) groups are recognized by an M6P receptor protein in the trans Golgi network that segregates the hydrolases and helps package them into budding transport vesicles that deliver their contents to endosomes. The M6P receptors shuttle back and forth between the trans Golgi network and the endosomes. The low pH in endosomes and the removal of the phosphate from the
Figure 13–46 The recognition of a lysosomal hydrolase. a glcnac phosphotransferase recognizes lysosomal hydrolases in the golgi apparatus. The enzyme has separate catalytic and recognition sites. The catalytic site binds both high-mannose n-linked oligosaccharides and udp-glcnac. The recognition site binds to a signal patch that is present only on the surface of lysosomal hydrolases. a second enzyme cleaves off the glcnac, leaving the mannose 6-phosphate exposed.
M6P group cause the lysosomal hydrolases to dissociate from these receptors, making the transport of the hydrolases unidirectional. A separate transport system uses clathrin-coated vesicles to deliver resident lysosomal membrane proteins from the trans Golgi network to endosomes.
TransporT InTo The cell froM The plasMa MeMbrane: endocyTosIs
The routes that lead inward from the cell surface start with the process of endocytosis, by which cells take up plasma membrane components, fluid, solutes, macromolecules, and particulate substances. Endocytosed cargo includes receptor– ligand complexes, a spectrum of nutrients and their carriers, extracellular matrix components, cell debris, bacteria, viruses, and, in specialized cases, even other cells. Through endocytosis, the cell regulates the composition of its plasma membrane in response to changing extracellular conditions.
In endocytosis, the material to be ingested is progressively enclosed by a small portion of the plasma membrane, which first invaginates and then pinches off to form an endocytic vesicle containing the ingested substance or particle. Most eukaryotic cells constantly form endocytic vesicles, a process called pinocytosis (“cell drinking”); in addition, some specialized cells contain dedicated pathways that take up large particles on demand, a process called phagocytosis (“cell eating”). Endocytic vesicles form at the plasma membrane by multiple mechanisms that differ in both the molecular machinery used and how that machinery is regulated.