Apical early endosomes

Macromolecules, such as proteins and peptides, are taken up by polarized epithelial cells by random pinocytosis, i.e., sampling of luminal fluid containing such molecules into apical early endosomes (AEE) as shown for MDCK cells in vitro (Leung et al. 2000). Further intracellular sorting is depicted in general terms in Fig. 3.3. Recycling to the apical surface or transcytosis is then mediated... 

Fig. 3.3 Intracellular sorting in epithelial cells after clathrin-mediated endocytosis. AEE apical early endosome ARE apical recycling endosome CE common endosome ...

However, not all proteins proceed directly to their eventual destination. Some proteins relocate from one plasma membrane compartment to another by means of trans-cytosis. Transcytosis involves endocytosis of selected proteins in one membrane compartment, followed by subsequent transport through early endosomes to recycling endosomes and finally translocation to a different membrane compartment, for example from the apical to the basolateral surfaces. Sorting at the TGN and endo-some recycling steps appear to have a primary role in the steady state distribution of proteins in different plasma membrane domains [47], However, selective retention of proteins at the plasma membrane by scaffolding proteins or selective removal may also contribute to normal distributions. Finally, microtubule-motor regulatory mechanisms have been discovered that might explain the specific delivery of membrane proteins to discrete plasma membrane domains [48]. 

Gentamicin is more toxic to LLC-PKj monolayers when exposed at the apical side, indicating a preferential uptake from the luminal membrane [136]. The uptake mechanism is proposed to be via megalin mediated endocytosis, a protein which is abundantly expressed in the proximal tubule [137]. A pathway delineated in LLC-PKl cells is proposed, whereby internalized aminoglycosides and other small molecular weight cationic compounds are transported from the early and late endosomes, through the Golgi complex. 

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