FIGURE 14-32 Delivery of plasma-membrane proteins to the lysosome interior for degradation. Early endosomes carrying endocytosed plasma-membrane proteins (blue) and vesicles carrying lysosomal membrane proteins (green) from the trans-Golgi network fuse with the late endosome, transferring their membrane proteins to the endosomal membrane (steps 1 and 2). Proteins to be degraded, such as those from the early endosome, are incorporated into vesicles that bud into the interior of the late endosome, eventually forming a multivesicular endosome containing many such internal vesicles (step 3). Fusion of a multivesicular endosome directly with a lysosome releases the internal vesicles into the lumen of the lysosome, where they can be degraded (step 4). Because proton pumps and other lysosomal membrane proteins normally are not incorporated into internal endosomal vesicles, they are delivered to the lysosomal membrane and are protected from degradation. See F. Reggiori and D. J. Klionsky, 2002, Eukaryot. Cell 1:11, and D. J. Katzmann et al., 2002, Nat. Rev. Mol. Cell Biol. 3:893.