Figure 218

Schematic diagram of a lysosome. This diagram shows a few selected lysosomal enzymes residing inside the lysosome and their respective substrates. The major lysosomal membrane-specific proteins, as well as a few other proteins associated with membrane transport, are also shown.

proteins transport protein nucleic acids transport protein

membrane impermeable to enzymes; contains specific lysosomal proteins, lamps, limps, and Igps glycosidases proteases lipases & H+ phospholipases glycosidases nucleases & related enzymes phosphatases h+

1 sulfatases membrane impermeable to enzymes; contains specific lysosomal proteins, lamps, limps, and Igps polysaccharides proton pump proton pump organic-linked phosphates organic-linked sulfates lysosomal membrane glycoproteins (Igps), and lysosomal integral membrane proteins (limps). The lamps, lgps, and limps represent more than 50% of the total membrane proteins in lysosomes and are highly glycosylated on the luminal surface. Sugar molecules cover almost the entire luminal surface of these proteins, thus protecting them from digestion by hydrolytic enzymes. The same family of proteins is also detected in late endo-somes. In addition, lysosomes and late endosomes contain proton (H+) pumps that transport H+ ions into the lysosomal lumen, maintaining a low pH (-4.7). The lysosomal membrane also contains transport proteins that transport the final products of digestion (amino acids, sugars, nucleotides) to the cytoplasm, where they are used in the synthetic processes of the cell or are exocy-tosed. All membrane proteins destined for lysosomes (and late endosomes) are synthesized in the rER, transported to the Golgi apparatus, and reach their destination by one of two pathways:

• In the constitutive secretory pathway, linips that exit the Golgi apparatus are delivered to the cell surface. From here, they are endocytosed and, via the early and late en-dosomal compartments, finally reach lysosomes (Fig. 2.19). This pathway does not require the M-6-P receptor targeting mechanism.

• In the Golgi-derived coated vesicle secretory pathway, limps, after sorting and packaging, exit the Golgi apparatus in clathrin-coated vesicles (see Fig. 2.19). These vesicles are delivered to the early and/or late endosome in a manner similar to that described for soluble lysosomal enzymes; thus, the M-6-P targeting mechanism is required for this pathway (see page 29).

Three different pathways deliver material for intracellular digestion in lysosomes

Depending on the nature of the digested material, different pathways deliver material for digestion within the lysosomes (Fig. 2.20). In the digestion process, most of the digested material comes from endocytotic processes; however, the cell also uses lysosomes to digest its own obsolete parts, nonfunctional organelles, and unnecessary molecules. Three pathways for digestion exist:

• Extracellular large particles such as bacteria, cell debris, and other foreign materials are engulfed in the process of phagocytosis. A phagosome, formed as the material is internalized within the cytoplasm, subsequently fuses with a lysosome to create a phagolysosome.

• Extracellular small panicles such as extracellular proteins, plasma membrane proteins, and ligand-receptor complexes are internalized by endocytosis and receptor-mediated endocytosis. These particles follow the endocytotic pathway through early and late endosomal compartments and are finally delivered to lysosomes for degradation.

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