Polarized membrane sorting

The combined effects of electroneutrality and the Donnan equilibrium permits us to evaluate the distribution of simple ions across a semipermeable membrane. If electrodes reversible to either the M+ or the X ions were introduced to both sides of the membrane, there would be no potential difference between them the system is at equilibrium and the ion activity is the same in both compartments. However, if calomel reference electrodes are also introduced into each compartment in addition to the reversible electrodes, then a potential difference will be observed between the two reference electrodes. This potential, called the membrane potential, reflects the fact that the membrane must be polarized because of the macroions on one side. It might be noted that polarized membranes abound in living systems, but the polarization there is thought to be primarily due to differences in ionic mobilities for different solutes rather than the sort of mechanism that we have been discussing. We return to a more detailed discussion of the electrochemistry of colloidal systems in Chapter 11. 

A number of substances have been discovered in the last thirty years with a macrocyclic structure (i.e. with ten or more ring members), polar ring interior and non-polar exterior. These substances form complexes with univalent (sometimes divalent) cations, especially with alkali metal ions, with a stability that is very dependent on the individual ionic sort. They mediate transport of ions through the lipid membranes of cells and cell organelles, whence the origin of the term ion-carrier (ionophore). They ion-specifically uncouple oxidative phosphorylation in mitochondria, which led to their discovery in the 1950s. This property is also connected with their antibiotic action. Furthermore, they produce a membrane potential on both thin lipid and thick membranes. 

There is not a unique binding site for all sorts of xenobiotics, but the compounds are intercalated in such a way into the membrane that they interact most favourably with the membrane components and with least perturbation. Some compounds, such as hydrophobic and neutral molecules, are actually dissolved in the membrane interior, whereas others exhibit more specific interactions in the polar region of the membrane. In general, interaction of the xenobiotics with the head groups leads to a stronger perturbation of the bilayer than intercalation in the membrane core [170]. 

Jareb M, Banker G. The polarized sorting of membrane proteins expressed in cultured hippocampal neurons using viral vectors. Neuron 1998 20 855-867. 

Laura RP, Ross S, Koeppen H, Lasky LA (2002) MAGI-1 A widely expressed, alternatively spliced tight junction protein. Exp Cell Res 275 155-170 Leung S-M, Ruiz WG, Apodaca G (2000) Sorting of membrane and fluid at the apical pole of polarized MDCK cells. Mol Biol Cell 11 2131-2150 Lipinski CA, Lombardo F, Dominy BW, Feeney PJ (1997) Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Del Rev 23 3-25... 

Schuck S, Simons K. Polarized sorting in epithelial cells raft clustering and the biogenesis of the apical membrane. J. Cell Sci. 2004 117 5955-5964. 

The endocytotic recycling pathways of polarized epithelial cells (Fig. 8.5), such as en-terocytes, are generally more complex than those in nonpolarized cells. In these entero-cytes there is a common recycling compartment (CRC) that receives molecules from both apical and basolateral membranes and is able to correctly return them to the appropriate membrane or membrane recycling compartment (ARC or BLRC) (25). The signals required for this sorting step have not been defined as of yet, but are presumably similar to... 

Several Pathways Sort Membrane Proteins to the Apical or Basolateral Region of Polarized Cells... 

Such direct basolateral-apical sorting has been investigated in cultured Madin-Darby canine kidney (MDCK) cells, a line of cultured polarized epithelial cells (see Figure 6-6). In MDCK cells infected with the influenza virus, progeny viruses bud only from the apical membrane, whereas in cells infected with vesicular stomatitis virus (VSV), progeny viruses bud only from the basolateral membrane. This difference occurs because the HA glycoprotein of influenza... 

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

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