Receptors on the surface of polarized epithelial cells can transfer specific macromolecules from one extracellular space to another by transcytosis. A newborn, for example, obtains antibodies from its mother’s milk (which help protect it against infection) by transporting them across the epithelium of its gut. The lumen of the gut is acidic, and, at this low pH, the antibodies in the milk bind to specific receptors on the apical (absorptive) surface of the gut epithelial cells. The receptor–antibody complexes are internalized via clathrin-coated pits and
Figure 13–55 The sequestration of endocytosed proteins into intralumenal vesicles of multivesicular bodies.
ubiquitylated membrane proteins are sorted into domains on the endosome membrane, which invaginate and pinch off to form intralumenal vesicles. The ubiquitin marker is removed and returned to the cytosol for reuse before the intralumenal vesicle closes. eventually, proteases and lipases in lysosomes digest all of the internal membranes. The invagination processes are essential for complete digestion of endocytosed membrane proteins: because the outer membrane of the multivesicular body becomes continuous with the lysosomal membrane, which is resistant to lysosomal hydrolases; the hydrolases, for example, could not digest the cytosolic domains of endocytosed transmembrane proteins, such as the egf receptor shown here, if the protein were not localized in intralumenal vesicles.
Figure 13–56 Sorting of endocytosed membrane proteins into the intralumenal vesicles of a multivesicular body.
a series of complex binding events passes the ubiquitylated cargo proteins sequentially from one escrT complex (escrT-0) to the next, eventually concentrating them in membrane areas that bud into the lumen of the endosome to form intralumenal vesicles. escrT-III assembles into expansive multimeric structures and mediates invagination. The mechanisms of how cargo molecules are shepherded into the vesicles and how the vesicles are formed without including the escrT complexes themselves remain unknown. escrT complexes are soluble in the cytosol, are recruited to the membrane sequentially as needed, and are then released back into the cytosol as the vesicle pinches off.
vesicles and are delivered to early endosomes. The complexes remain intact and are retrieved in transport vesicles that bud from the early endosome and subsequently fuse with the basolateral domain of the plasma membrane. On exposure to the neutral pH of the extracellular fluid that bathes the basolateral surface of the cells, the antibodies dissociate from their receptors and eventually enter the baby’s bloodstream.
The transcytotic pathway from the early endosome back to the plasma membrane is not direct. The receptors first move from the early endosome to the recycling endosome. The variety of pathways that different receptors follow from early endosomes implies that, in addition to binding sites for their ligands and binding sites for coated pits, many receptors also possess sorting signals that guide them into the appropriate transport pathway (Figure 13–58).