The permeability of intercellular junctions formed between animal cells

1. The literature concerning the structure of intercellular junctions is reviewed. Particular attention is paid to the gap junction which is generally believed to be the membrane specialization responsible for intercellular communication. The permeability of communicating junctions' and the modulation of junctional communication are critically reviewed. The possible roles of junctional communication between cells are discussed. 2. The permeability of junctions formed between animal cells in culture has been examined by following the intercellular movement (or lack of movement) of a selection of endogenous molecules between cells in contact. 3. Using modifications of established methods it was shown that intermediate metabolites derived from choline (phosphoryl choline and CDP-choline) were readily exchanged between cells in contact if the cells formed permeable intercellular junctions. However, phospholipids derived from choline were not exchanged between cells joined by such junctions. 4. By a new approach, dependent upon the cell type specific rate of 2-deoxy-glucose-6-phosphate loss from cells, it was shown that this sugar phosphate is exchanged between cells joined by permeable intercellular junctions but not between cells which are unable to form these junctions. It was also shown that these junctions might be permeable to intermediate metabolites, but not macromolecules (glycoproteins), derived from glucosamine. 5. The ability of cells to incorporate labelled formate was used as a measure of their folate content. This allowed the development of a novel method which showed that cellular folates are transferred from untreated cells to folate starved cells if the two cell types are joined by permeable intercellular junctions. However, the rate of transfer of cellular folates through these junctions appeared to be much slower than for other molecules. Using cells which had a lesion in folate metabolism, it was shown that this slow rate of transfer could be due to the impermeability of intercellular junctions to the pentaglutamate derivative of folate (which is the predominant form of folate in mammalian cells). 6. The permeability of intercellular junctions to amino acids was examined by using a cell type which was auxotrophic for proline. It was shown that these cells lost their dependence on exogenous proline for growth when cultured with junction forming cells but not with non-junction forming cells. The ability of wild-type, junction forming cells to support the growth of the auxotrophic cells was shown not to be due to an extracellular pathway of proline transfer. 7. The ability of different cell types to form permeable intercellular junctions was measured using two different methods. The two methods gave comparable results and showed that different cell types can vary greatly in their ability to allow junctional exchange of metabolites. 8. The significance of the observations made in the course of this work are critically discussed and related to other published work on junctional communication. It is proposed that populations of cells which are joined by gap junctions will tend to form 'functional syncyctia' and this property of gap junctions may have an important role in the evolution of animal tissues. 9. The properties of two mutant cell types apparently lacking thymidine kinase were examined. These cells showed characteristic reduced ability to incorporate thymidine at low exogenous thymidine concentrations (10