Targeting Proteins to the Lysosome

One of the best-understood examples of sorting in the trans-Golgi network is lysosomal targeting (Fig. 10.11). Proteins that are destined for the lysosome are synthesized on the rough endoplasmic reticulum and therefore, like all proteins synthesized here, have a mannose-containing oligosaccharide added. Because they do not have an endoplasmic reticulum retention signal such as KDEL, they are transported to the Golgi apparatus. There proteins

Golgi apparatus

(pre) lysosome

Golgi apparatus

(pre) lysosome

addition of a phosphate group to a mannose group on the polypeptide receptor

Figure 10.11. Targeting of protein to the lysosome.

membrane and receptor decycling addition of a phosphate group to a mannose group on the polypeptide receptor

Figure 10.11. Targeting of protein to the lysosome.

destined for the lysosome are modified by phosphorylation of some of their mannose residues to form mannose-6-phosphate (Fig. 2.11 on page 32). Once the proteins reach the trans-Golgi network, specific receptors for mannose-6-phosphate recognize this sorting signal and cause the proteins to be packaged into vesicles that are transported to the lysosome, where they fuse. In the low pH (5.0) environment of the lysosome, the lyso-somal protein can no longer bind to its receptor. The phosphate group is removed by a phosphatase. Vesicles containing the receptor bud off from the lysosome and deliver the mannose-6-phosphate receptors back to the trans-Golgi network.

The function of the lysosome is to degrade unwanted materials. To carry out this function, an inactive or primary lysosome fuses with a vesicle containing the material to be digested. This makes a secondary lysosome. The vesicles with which primary lysosomes fuse may be bringing materials in from outside the cell or they may be vesicles made by condensing a membrane around worn out or unneeded organelles in the cells own cytoplasm. The latter are sometimes called autophagic vacuoles. Some materials may not be digestible and remain in the lysosome for the lifetime of the cell. These small dense remnant lysosomes are called residual bodies.

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