Focal adhesions are sites of tight adhesion to the underlying extracellular matrix developed by cells in culture. They provided a structural link between the actin cytoskeleton and the extracellular matrix and are regions of signal transduction that relate to growth control. The assembly of focal adhesions is regulated by the GTP-binding protein Rho. Rho stimulates contractility which, in cells that are tightly adherent to the substrate, generates isometric tension. In turn, this leads to the bundling of actin filaments and the aggregation of integrins (extracellular matrix receptors) in the plane of the membrane. The aggregation of integrins activates the focal adhesion kinase and leads to the assembly of a multicomponent signaling complex.

/pdf/focal-adhesions-contractility-and-signaling-ij3wyc7tuo.pdf

Focal adhesions, contractility, and signaling

Lang, Florian, Gillian L. Busch, Markus Ritter, Harald Volkl, Siegfried Waldegger, Erich Gulbins, and Dieter Haussinger. Functional Significance of Cell Volume Regulatory Mechanisms. Physiol. Rev. ...

Functional Significance of Cell Volume Regulatory Mechanisms

Metastases do not result from random survival of cells released from the primary tumour but from the selective growth of specialised subpopulations of highly metastatic cells endowed with specific properties that befit them to complete each step of the metastatic process.

/pdf/the-pathogenesis-of-cancer-metastasis-50jty52rxh.pdf

The pathogenesis of cancer metastasis

The modification of mammalian membrane polyunsaturated fatty acid composition in relation to membrane fluidity and function

Simple and complex carbohydrates (glycans) have long been known to play major metabolic, structural and physical roles in biological systems. Targeted microbial binding to host glycans has also been studied for decades. But such biological roles can only explain some of the remarkable complexity and organismal diversity of glycans in nature. Reviewing the subject about two decades ago, one could find very few clear-cut instances of glycan-recognition-specific biological roles of glycans that were of intrinsic value to the organism expressing them. In striking contrast there is now a profusion of examples, such that this updated review cannot be comprehensive. Instead, a historical overview is presented, broad principles outlined and a few examples cited, representing diverse types of roles, mediated by various glycan classes, in different evolutionary lineages. What remains unchanged is the fact that while all theories regarding biological roles of glycans are supported by compelling evidence, exceptions to each can be found. In retrospect, this is not surprising. Complex and diverse glycans appear to be ubiquitous to all cells in nature, and essential to all life forms. Thus, >3 billion years of evolution consistently generated organisms that use these molecules for many key biological roles, even while sometimes coopting them for minor functions. In this respect, glycans are no different from other major macromolecular building blocks of life (nucleic acids, proteins and lipids), simply more rapidly evolving and complex. It is time for the diverse functional roles of glycans to be fully incorporated into the mainstream of biological sciences.

/pdf/biological-roles-of-glycans-zowb8sw07y.pdf

Biological Roles of Glycans

http://www.jbc.org/content/249/10/3116.full.pdf

Wheat Germ Agglutinin MOLECULAR CHARACTERISTICS AND SPECIFICITY FOR SUGAR BINDING

Publisher Summary This chapter outlines several characteristics of tumor cells that are indicative of their having altered surface membranes. Agglutinins enable to monitor cell surface alterations. The discovery that the surface of normal cells during mitosis is in several ways analogous to that of transformed cells is enlightening as it suggests the existence of a critical switching point in the cell cycle—that is, transformation can operate like the throwing of a switch that sidetracks the cell from the completion of the normal cycle with eventual shutoff in G1 and keeps it oriented toward continual division. There is a critical point in the cell cycle when any normal cell can either be steered toward quiescence or switched over toward malignant growth and transformation. Evidence from the studies described in the chapter indicates that the cell membrane plays a role in this modulation of growth control, but much more research is still needed before it can definitively be decided whether the membrane alterations observed are only correlates or whether they do have a causal role.

Tumor cell surfaces: general alterations detected by agglutinins.

Permeabilized bovine adrenal chromaffin cells have been used to characterize the MgATP requirement of processes preceding exocytosis. Incubation of primary cultures with the membrane-permeable phenylarsine oxide (PAO) at 20 microM inhibited the phosphorylation of phosphatidylinositol (PtdIns) and completely blocked secretion. This block could be reversed by addition of 2,3-dimercaptopropanol to the permeabilized cells. Simultaneous addition of [gamma32P]ATP and 2,3-dimercaptopropanol permitted a comparison between recovery of secretion and phosphorylation of intracellular components. Recovery of secretion closely correlated with phosphorylation of PtdIns and PtdIns4P. Subcellular fractionation of permeabilized cells after recovery of secretion revealed that the majority of newly phosphorylated PtdIns4P was localized on the chromaffin granules. In accordance with these results, PtdIns 4-kinase activity was found in protein extracts of permeabilized cells as well as associated with purified chromaffin granules, sensitive in both cases to PAO. Additionally, PtdIns 4-kinase activity in these two assays was inhibited by quercetin. In permeabilized cells, quercetin decreased the levels of labeled PtdIns4P and Ptdlns(4,5)P2 and inhibited secretion. Our data suggest that a chromaffin granule-associated PtdIns 4-kinase acts in the priming of exocytosis.

https://www.embopress.org/doi/pdf/10.1002/j.1460-2075.1996.tb00563.x

Chromaffin granule-associated phosphatidylinositol 4-kinase activity is required for stimulated secretion.

THE cell surface may be involved in the metastatic process of cancer cells1. To determine whether membrane properties influence or reflect the metastasising capacity, it is essential to have metastasising and non-metastasising variants of the same tumour. Lectins which bind specifically to surface carbohydrates2 have been used successfully as selective agents to obtain cells with membrane carbohydrate alterations3–5. We have selected variants of melanoma cells for surface differences in using toxic concentrations of lectins in the hope that such variants would exhibit different metastasising capacities. We report here the isolation of variants from metastasising melanoma cells resistant to toxic concentrations of wheat germ agglutinin (WGA). These variants show reduced to a loss of metastasising capacity and altered surface properties.

Non-metastasising variants selected from metastasising melanoma cells

SPONGE cells dissociated by means of seawater containing no calcium or magnesium release a large molecular factor (AF) which is required for specific reaggregation at 4° C into multicellular agglomerations the size of small sponges1. The function of the aggregation factor (AF) in Microciona prolifera is dependent on a specific carbohydrate2. Here we describe the isolation of a second macromolecular component, other than AF, which is necessary for reaggregation, and which seems to remain on the surface of the cell after removal of the aggregation factor, and to interact with intercellular AF. Until its function is clearly understood, we shall describe it as a baseplate.

Max M. Burger

Papers

Wheat Germ Agglutinin MOLECULAR CHARACTERISTICS AND SPECIFICITY FOR SUGAR BINDING

Tumor cell surfaces: general alterations detected by agglutinins.

Chromaffin granule-associated phosphatidylinositol 4-kinase activity is required for stimulated secretion.

Non-metastasising variants selected from metastasising melanoma cells

Two component system for surface guided reassociation of animal cells.