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“...The assumption that the cytoplasm is a well-stirred solution contained within a neatly defined plasma membrane 10 nm thick was a very useful one to measure membrane fluxes and electrical phenomena, yet it is not adequate to understand polarity and TJs. Electron microscopy and cytochemistry show that the cell is overstuffed with organelles, fixed electric charges and polar sites able to establish hydrogen bonds, so no molecule, not even water, is free to diffuse in the cytoplasm. In this respect, it is extremely improbable – actually, impossible – that a given protein species would achieve a homogeneous distribution neither all over the cell nor in the plasma membrane. Nature does not rely on random distributions and fortuitous encounters but distributes molecular species according to their character. Furthermore, proteins do not just carry signals but are themselves signals due to a sequence, a configuration, a distribution of electric charges, anchoring to a lipid or another protein, that are recognized and sent to the cellular location where they should reside. Once there, further modifications due to phosphorylation, contact with a given subunit, or the influence of an ion that has just increased its concentration, suffice to make it appear as a different molecule and, accordingly, transferred to some other specific location in the cell, secreted, degraded, etc. In this respect, polarity depends on addressing signals that are interpreted by mechanisms, that deliver the molecule accordingly to a specify target, and a scaffold of molecules that retains it in position. TJs and polarity are not “things”, but frozen images of vertiginous processes of exchange of proteins between organelles. ...“ Cereijido M, Contreras RG, Shoshani L, Flores-Benitez D, Larre I. “Tight junction and polarity interaction in the transporting epithelial phenotype.“ Biochim Biophys Acta. 2008 Mar;1778(3):770-93.
