Competition between cell-substratum interactions and cell-cell interactions.

Clusterin, a glycoprotein which elicits the aggregation of a wide variety of cells (Fritz, I. B., and Burdy, K.:J. Cell Physiol., 140:18-28, 1989), has been utilized to investigate some of the factors modulating the competition between cell-substratum interactions and cell-cell interactions. We compared the responses to clusterin by anchorage-independent cells (erythrocytes) with those by anchorage-dependent TM4 cells (a cell line derived from neonatal mouse testis cells). Cells were maintained in culture in the presence of various substrata chosen to enhance cell-substratum interactions (laminin-coated wells), or to diminish cell-substratum interactions (agarose-coated wells). Results obtained showed that the aggregation of erythrocytes elicited by clusterin was independent of the nature of the substratum. In contrast, clusterin addition resulted in aggregation of anchorage-dependent TM4 cells only when TM4 cell-substratum interactions were weak. Thus, clusterin did not aggregate TM4 cells plated upon a laminin substratum, but readily aggregated TM4 cells plated upon an agarose-coated substratum, independent of the sequence of addition of cells and clusterin to the culture dish. We utilized YIGSR, a peptide which competes with laminin for laminin receptors, to determine the possible role of laminin receptors on TM4 cells in the competition between cell-substratum interactions and cell-cell interactions. The presence of YIGSR did not alter responses of erythrocytes to clusterin under all conditions examined. In contrast, the responses of TM4 cells to clusterin were greatly changed. YIGSR addition resulted in the inhibition of aggregation of TM4 cells otherwise elicited by clusterin. YIGSR also prevented attachment of TM4 cells to a laminin-coated surface, but this was reversed by the presence of clusterin. We discuss the possible roles of clusterin and laminin in altering the balance in the competition between cell to cell interactions and cell to substratum interactions.     

Tumor-stroma interactions

The importance of stromal cells and the factors that they express during cancer initiation and progression has been highlighted by recent literature. The cellular components of the stroma of epithelial tissues are well-recognized as having a supportive role in carcinogenesis, where the initiating mutations of a tumor originate in the epithelial cells. The use of mouse models and xenografts suggests that mutations in the stromal fibroblasts can also initiate epithelial tumors. Many of these tumors result from the alteration of paracrine growth factor pathways that act on the epithelia. However, the tissue specificity of the responses to the growth factors is a mystery not yet solved.     

Picornavirus-receptor interactions

Many picornaviruses use cell-surface molecules belonging to the immunoglobulin superfamily (IgSF) as their cellular receptors. These molecules usually consist of tandem repeats of between two and five Ig-like domains whose amino-terminal domains (D1) interact with invading viruses, with their carboxy-terminal sections comprising a transmembrane and a short cytoplasmic region. Most rhino- and enteroviruses, belonging to the Picornavirus family, use a canyon-like feature on their surface to attach to cellular receptors. Binding into the canyon destabilizes the virus and thus initiates the uncoating process. By contrast, non-IgSF molecules, when used by picornaviruses as receptors, bind outside the canyon and do not cause viral instability.     

Carotenoid-radical interactions

Carotenoids have been reported to react with virtually any radical species likely to be encountered in a biological system. The products of such reactions are frequently short-lived radical species that can decay to more stable products. In some cases, stable adducts can be observed, but in the majority of interactions with radicals, carotenoids break down to degradation products very similar to what is seen with oxidative degradation. It is only recently that the biological activity of these breakdown products has begun to be investigated.     

Lipid-protein interactions

Intrinsic membrane proteins are solvated by a shell of lipid molecules interacting with the membrane-penetrating surface of the protein; these lipid molecules are referred to as annular lipids. Lipid molecules are also found bound between transmembrane α-helices; these are referred to as non-annular lipids. Annular lipid binding constants depend on fatty acyl chain length, but the dependence is less than expected from models based on distortion of the lipid bilayer alone. This suggests that hydrophobic matching between a membrane protein and the surrounding lipid bilayer involves some distortion of the transmembrane α-helical bundle found in most membrane proteins, explaining the importance of bilayer thickness for membrane protein function. Annular lipid binding constants also depend on the structure of the polar headgroup region of the lipid, and hotspots for binding anionic lipids have been detected on some membrane proteins; binding of anionic lipid molecules to these hotspots can be functionally important. Binding of anionic lipids to non-annular sites on membrane proteins such as the potassium channel KcsA can also be important for function. It is argued that the packing preferences of the membrane-spanning α-helices in a membrane protein result in a structure that matches nicely with that of the surrounding lipid bilayer, so that lipid and protein can meet without either having to change very much.     

Plant-nematode interactions

Root-knot nematodes and cyst nematodes are obligate, biotrophic pathogens of numerous plant species. These organisms cause dramatic changes in the morphology and physiology of their hosts. The molecular characterization of induced plant genes has provided insight into the plant processes that are usurped by nematodes as they establish their specialized feeding cells. Recently, several gene products have been identified that are secreted by the nematode during parasitism. The corresponding genes have strong similarity to microbial genes or to genes that are found in nematodes that parasitize animals. New information on host resistance genes and nematode virulence genes provides additional insight into this complex interaction.     

Aminoglycoside-RNA interactions

The structural and physico-chemical parameters promoting the binding of aminoglycosides to RNAs are becoming clear. The strength of the interaction is dominated by electrostatics, with the positively charged aminoglycosides displacing metal ions. Although aminoglycosides inhibit most known ribozymes, aminoglycosides or polyamines are able to catalyze specific RNA cleavage in the absence of metal ions.     

Thalamocortical interactions

Glutamatergic pathways dominate information processing in the brain, but these are not homogeneous. They include two distinct types: Class 1, which carries the main information for processing, and Class 2, which serves a modulatory role. Identifying the Class 1 inputs in a circuit can lead to a better understanding of its function. Also, identifying Class 1 inputs to a thalamic nucleus tells us its main function (e.g. the lateral geniculate nucleus, or LGN, is the relay of retinal Class 1 input), and such identification leads to a division of thalamic relays into first and higher order: the former receives Class 1 inputs from subcortical sources; the latter, from layer 5 of cortex, which it then relays to another cortical area. When a cortical area directly connects with another, it often has a parallel, transthalamic connection through these higher order relays. This leads to a novel appreciation of cortical functioning and raises many new questions.     

Bacterial interactions

The review deals with specific features of interactions in microbial biocenoses. The subdivision of the mechanisms of microbial interactions in associations into direct and indirect ones is proposed. The formation of intercellular contacts and matrix belongs to one group of mechanisms, the second group includes the products of metabolism (changes in the physical and chemical composition of the medium, specific growth regulators) and secreted factors (antibacterial substances, pheromones and signal molecules, vitamins, specific mediators). The applied aspects of the knowledge of microbial interactions in the human body are presented.     

Protein-biotin interactions

The three-dimensional structures of several biotin-binding proteins are now known, giving insights into the molecular architecture of the binding sites for biotin. In combination with biochemical and computational approaches, these structural insights provide the basis for our present understanding of biotin—protein interactions which, in some cases, give rise to spectacular binding constants.