Basolateral plasma membrane proteins

Le Bivic, A., Real, F. X., and Rodriguez-Boulan, E. (1989) Vectorial targeting of apical and basolateral plasma membrane proteins in a human adenocarcinoma epithelial cell line. Proc. Natl. Acad. Sci. USA 86, 9313-9317. 

Many cells have an asymmetric structure because of the necessity for function (Drubin and Nelson, 1996). For example, (the outer surface of) the plasma membrane of epithelial cells is fenced by a tight junction so that the lipids are separated between the apical part and the basolateral part (Fig. 9) (Eaton and Simons, 1995). Therefore, some molecular mechanisms must exist to sort the plasma membrane proteins into these two parts. Some signals related to the secretory/endocytic pathways have been found important (Matter and Mellman, 1994). Their details are not described here because the area is too specific for predictive purposes. 

After the initial binding to the anionic phospholipids of the PTC, the aminoglycoside molecule is quickly transferred to the transmembrane protein megalin and endocytosed [42, 43, 48-50, 52-59, 66-68, 72, 73]. Aminoglycosides enter the PTC on either the apical or basolateral plasma membrane via receptor-mediated endocytosis. and are ultimately sequestered in the same endosomal compartment [68]. In an experiment with LLC-PKl cells. Ford et al. demonstrated that aminoglycosides were internalized equally across the apical and basolateral membranes by receptor-mediated endocytosis. This was followed by colocalization within the lysosomal compartment and similar magnitudes of cellular dysfunction [68]. 

At least 11 different mammalian AQP have now been identified, of which seven (AQPl, -2, -3, -4, -6, -7, -8) are expressed in the Iddney. Many of these also have extra-renal expression sites (e.g, AQPl may be unportant in fluid removal across the peritoneal membrane). Two asparagine-prohne-alanine sequences in the molecule are thought to interact in the membrane to form a pathway for water translocation. AQPl is found in the proximal tubule and descending thin limb of the loop of Henle and constitutes almost 3% of total membrane protein in the kidney. It appears to be constitutively expressed and is present in both the apical and basolateral plasma membranes, representing the entry and exit ports for. water transport across the cell, respectively. Approximately 70% of water reabsorption occurs at this site, predominantly via a transcellular (i.e., AQPl) rather than a paracellular route. Water reabsorption in the proximal tubule passively follows sodium reabsorption, so that the fluid entering the loop of Henle is still almost isosmotic with plasma. 

The already mentioned proteins OCTI and OCT3 transport small cationic substances, such as tetraalkyl ammonium compounds, polyamines such as spermine, monoamino-neurotransmitters, or N-methyl-nicotinamide across the basolateral plasma membrane [56]. OCTs play a key role in the distribution of cationic drugs and, therefore, drug interactions at the transporter level may become clinically relevant, as compounds with high affinity, such as prazosin or phenox-ybenzamine, may affect the excretion of other substrates. Certain liver diseases or obstructive cholestasis may result in alterations of hepatic clearance via these transporters. In rats, a 7-day bile duct ligation resulted in a marked downregulation of Octi and an increased hepatic accumulation of the Octi substrate tetraethylammonium [57]. 

The apical and basolateral plasma membrane domains of epithelial cells contain different transport proteins and carry out quite different transport processes. 

FIGURE 17-26 Sorting of proteins destined for the apical and basolateral plasma membranes of polarized cells. 

In hepatocytes and some other polarized cells, all plasma-membrane proteins are directed first to the basolateral membrane. Apically destined proteins then are endocytosed and moved across the cell to the apical membrane (transc a osis). 

Figure 21.1 Placement of a functional sodium iodide symporter (NIS) at the cell s basolateral surface is a complex process involving a number of molecular biological steps. The gene is first translated into mRNA. The mRNA is then translated into a protein, which must then be properly folded, glycosylated and otherwise modified, and successfully trafficked to and inserted into the cell s basolateral plasma membrane.

Multi-drug resistance associated protein (MRP), member of the ATP binding Cassette transporter proteins, is particularly involved in glutathione-conjugates detoxification. In human bronchial ciliated ceUs MRP mRNA immunostaining was observed at the basolateral plasma membrane (Br6-CHOT et al. 1997). 

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]. 

Fig. 6.2. Model for how FcRn rescues IgG from catabolism by recycling and transcytosis. IgG and many other soluble proteins are present in extracellular fluids. Vascular endothelial cells are active in fluid phase endocytosis of blood proteins. Material taken up by these cells enters the endosomes where FcRn is found as an integral membrane protein. The IgG then binds FcRn in this acidic environment. This binding results in transport of the IgG to the apical plasma membrane for recycling into the circulation, or to the basolateral membrane for transcytosis into the extracellular space. Exposure to a neutral pFI in both locations then results in the release of IgG. The remaining soluble proteins are channeled to the lysosomal degradation pathway.

The cells lining the lumen of the intestine are polarized, that is they have two distinct sides or domains which have different lipid and protein compositions. The apical or brush border membrane facing the lumen is highly folded into microvilli to increase the surface area available for the absorption of nutrients. The rest of the plasma membrane, the basolateral surface, is in contact with neighboring cells and the blood capillaries (Fig. 5). Movement between adjacent epithelial cells is prevented by the formation of tight junctions around the cells near the apical domain. Thus any nutrient molecules in the lumen of the intestine have to pass through the cytosol of the epithelial cell in order to enter the blood. 

The apical membrane of a polarised cell is that part of the plasma membrane that forms its luminal surface, particularly so in the case of epithelial and endothehal cells. The basolateral membrane of a polarised cell refers to that part of the plasma membrane that forms its basal and lateral surfaces. Proteins are free to move from the basal to lateral surfaces, but not to the apical surface tight junctions, which join epithehal cells near their apical surfaces, prevent migration of proteins to the apical surface. The apical surface is therefore distinct from the basal/lateral surfaces. 

Intestinal absorption of toxin across the brush border probably involves toxin recognition by a plasma membrane anchored protein and efficient apical-to-basolateral transport across the intestinal epithelium. 

FIGURE 2.49 An absorptive cell of the viUus. The part of the plasma membrane facing the lumen is the apical membrane, whereas that facing the blood supply is the basal and lateral (basolateral) membrane. The membrane-bound proteins used to mediate the uptake of a variety of nutrients requires the simultaneous co-transport of sodium ions. The diagram reveals that the transport of glucose cind amino acids is dependent on sodium ions. Sodium-independent transport systems also exist for many nutrients. The sodium depicted in the figure is supplied by intestinal secretions and need not be supplied by any particular diet. 

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