The Plasma Membrane

TABLE I. The Sialic Acid Present in the Various Organelles of Cells 

Ehrlich ascites carcinoma Whole cells 100 Wallach and Eylar, 

L cell (Mouse fibroblast) Whole cell 100 Click c/a/., 1971 

L-fucose D-mannose D-galactose D-hexosamine Sialic acid Cells N = 16 

TABLE III. Percentage of Total Sialic Acid of Intact Cell Removed by Treatment with V. cholerae Neuraminidase 

The application of other techniques, however, led to a rather different conception of the plasma membrane, as in Fig. 5.5. Freeze-etching sharpened the image of the outer surface of the membrane, and freeze-fracture revealed planes of fracture within the membrane (both techniques used 

4 Classical representation of plasma membrane (Davson and Danielli, 1952.) 

5 Contemporary representation of plasma membrane (Singer and Nicolson, 1972.) 

This fluid-mosaic membrane model allows proteins their freedom to diffuse in the plane of the lipid membrane and hence to become distributed over the cell surface in a pattern that is sometimes random and sometimes homogeneous (Singer and Nicolson, 1972). There are (a) integral proteins running perpendicularly to the plane of the lipid layer, some passing right through the bilayer, others only half way, and (b) extrinsic proteins that have become adsorbed on one or other of the surfaces of the bilayer and are easily lost. 

Some of the proteins that span the bilayer seem to be coiled rods, as detected by freeze fracture, whereas others appear to be globular (see Fig. 5.5). Most, possibly all, of these penetrating proteins have an attached carbohydrate molecule, which remains on the cytoplasmic side, apparently serving as a hydrophilic anchor for the protein. Membrane proteins at the site of junction between two cells appear to have little mobility. 

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Dam]anovich S, Gaspar R and Pier C 1997 Dynamic receptor superstructures at the plasma membrane Q. Rev. Biophys. 30 67-106... 

Fig. 1. The GP Ib-IX-V complex. The complex consists of seven transmembrane polypeptides denoted GP Iba (mol wt 145,000), GP IbP (mol wt 24,000), GPIX (mol wt 17,000) and GP V (mol wt 82,000), in a stoichiometry of 2 2 2 1. The hatched region represents the plasma membrane. The area above the hatched region represents the extracellular space that below represents the cytoplasm. The complex is a major attachment site between the plasma membrane and the cytoskeleton. Two molecules associated with the cytoplasmic domain are depicted a 14-3-3 dimer, which may mediate intracellular signaling, and actin-binding protein, which connects the complex to the cortical cytoskeleton and fixes its position and influences its function.

Dmg receptors are chemical entities which are typically, but not exclusively, small molecules that interact with cellular components, frequently at the plasma membrane level (1,2). There are many types of receptors heat, light, immune, hormone, ion channel, toxin, and vims are but a few that can excite a cell. The receptor concept can be appHed generally to signal recognition processes where a chemical or physical signal is recognized. This recognition is translated into response (Fig. 3) and the process can be seen as a flow of information. 

Ion Channels. The excitable cell maintains an asymmetric distribution across both the plasma membrane, defining the extracellular and intracellular environments, as well as the intracellular membranes which define the cellular organelles. This maintained a symmetric distribution of ions serves two principal objectives. It contributes to the generation and maintenance of a potential gradient and the subsequent generation of electrical currents following appropriate stimulation. Moreover, it permits the ions themselves to serve as cellular messengers to link membrane excitation and cellular... 

Fig. 18. Schematic representation of cycling of low density Hpoprotein (LDL) receptors from the plasma membrane to the cell interior.

Fig. 12. Model for the P-adenergic receptor. It is proposed that the receptor possesses seven hydrophobic heUces that span the plasma membrane and are connected by alternating extracellular and intracellular loops (79). The site of glycosylation is represented as CHO. Reprinted with permission from Elsevier...

A 2-h incubation with another PGE2 analogue, nocloprost (9P-chloro-DMPG) protects normal human fibroblasts but has no effect on the survival of colon adenocarcinoma cells exposed to 10 Gy (1000 rad) (218). Nocloprost protects against radiation-induced DSBs in normal cells but not in tumor cells. Moreover, incubation using nocloprost for 2 h after irradiation enhances the rate of DSB rejoining in fibroblasts but not in adenocarcinoma cells. These data possibly reflect a different distribution of PG receptors on the plasma membrane of the two cell types. 

Finally, some amphiphilic sweeteners, eg, aspartame, saccharin, and neohesperidin dihydrochalcone, have been shown to be capable of stimulating a purified G-protein direcdy in an in vitro assay (136). This suggests some sweeteners may be able to cross the plasma membrane and stimulate the G-protein without first binding to a receptor. This type of action could explain the relatively longer response times and the lingering of taste associated with many high potency sweeteners. 

Three hormones regulate turnover of calcium in the body (22). 1,25-Dihydroxycholecalciferol is a steroid derivative made by the combined action of the skin, Hver, and kidneys, or furnished by dietary factors with vitamin D activity. The apparent action of this compound is to promote the transcription of genes for proteins that faciUtate transport of calcium and phosphate ions through the plasma membrane. Parathormone (PTH) is a polypeptide hormone secreted by the parathyroid gland, in response to a fall in extracellular Ca(Il). It acts on bones and kidneys in concert with 1,25-dihydroxycholecalciferol to stimulate resorption of bone and reabsorption of calcium from the glomerular filtrate. Calcitonin, the third hormone, is a polypeptide secreted by the thyroid gland in response to a rise in blood Ca(Il) concentration. Its production leads to an increase in bone deposition, increased loss of calcium and phosphate in the urine, and inhibition of the synthesis of 1,25-dihydroxycholecalciferol. 

Adenosine, 6-amino-9-P-ribofuranosyl-9-ff-purine (see Table 1), is an endogenous nucleoside found in all ceUs of the body. Its ubiquitousness suggests that adenosine functions as an autocoid and that its actions are mediated by specific receptors on the plasma membranes of all ceUs. 

PH-20, a guinea pig sperm protein of 64 kD, is present on both the plasma membrane and inner acrosomal membrane of sperm. It is essential for adhesion of sperm to the zona peUucida, the initial step in the fertilization process. Active immunization with PH-20 causes infertility in both male and female guinea pigs for a period ranging from 6 to 15 months (120). 

In addition to binding to sialic acid residues of the carbohydrate side chains of cellular proteins that the virus exploits as receptors, hemagglutinin has a second function in the infection of host cells. Viruses, bound to the plasma membrane via their membrane receptors, are taken into the cells by endocytosis. Proton pumps in the membrane of endocytic vesicles that now contain the bound viruses cause an accumulation of protons and a consequent lowering of the pH inside the vesicles. The acidic pH (below pH 6) allows hemagglutinin to fulfill its second role, namely, to act as a membrane fusogen by inducing the fusion of the viral envelope membrane with the membrane of the endosome. This expels the viral RNA into the cytoplasm, where it can begin to replicate. 

This fusogenic activity of influenza hemagglutinin is frequently exploited in the laboratory. If, for example, the virus is bound to cells at a temperature too low for endocytosis and then the pH of the external medium is lowered, the hemagglutinin causes direct fusion of the viral envelope with the plasma membrane infection is achieved without endocytosis. Similarly, artificial vesicles with hemagglutinin in their membrane and other molecules in their lumen can be caused to fuse with cells by first allowing the vesicles to bind to the plasma membrane via the hemagglutinin and then lowering the pH of the medium. In this way the contents of the vesicles are delivered to the recipient cell s cytoplasm. 

Prokaryotic cells have only a single membrane, the plasma membrane or cell membrane. Because they have no other membranes, prokaryotic cells contain no nucleus or organelles. Nevertheless, they possess a distinct nuclear area where a single circular chromosome is localized, and some have an internal membranous structure called a mesosome that is derived from and continuous with the cell membrane. Reactions of cellular respiration are localized on these membranes. In photosynthetic prokaryotes such as the cyanobacteria,... 

Cell membrane Roughly 50 50 lipid protein as a 5-um-thick The plasma membrane is a selectively... 

Cells make use of many different types of membranes. All cells have a cytoplasmic membrane, or plasma membrane, that functions (in part) to separate the cytoplasm from the surroundings. In the early days of biochemistry, the plasma membrane was not accorded many functions other than this one of partition. We now know that the plasma membrane is also responsible for (1) the exclusion of certain toxic ions and molecules from the cell, (2) the accumulation of cell nutrients, and (3) energy transduction. It functions in (4) cell locomotion, (5) reproduction, (6) signal transduction processes, and (7) interactions with molecules or other cells in the vicinity. 

Even the plasma membranes of prokaryotic cells (bacteria) are complex (Figure 9.1). With no intracellular organelles to divide and organize the work, bacteria carry out processes either at the plasma membrane or in the cyto-... 

FIGURE 9.32 Proteoglycans serve a variety of functions on the cytoplasmic and extracellular surfaces of the plasma membrane. Many of these functions appear to involve the binding of specific proteins to the glycosaminoglycan groups. 

FIGURE 10.37 Gap Juoctioos consist of hexameric arrays of cylindrical protein subunits in the plasma membrane. The subunit cylinders are tilted with respect to the axis running through the center of the gap Junction. A gap Junction between cells is formed when two hexameric arrays of subunits in separate cells contact each other and form a pore through which cellular contents may pass. Gap Junctions close by means of a twisting, sliding motion in which the subunits decrease their tilt with respect to the central axis. Closure of the gap Junction is Ca -dependent. 

Fructose is present outside a cell at 1 /iM concentration. An active transport system in the plasma membrane transports fructose into this cell, using the free energy of ATP hydrolysis to drive fructose uptake. Assume that one fructose is transported per ATP hydrolyzed, that ATP is hydrolyzed on the intracellular surface of the membrane, and that the concentrations of ATP, ADP, and Pi are 3 mM, 1 mM, and 0.5 mM, respectively. T = 298 K. What is the highest intracellular concentration of fructose that this transport system can generate Hint Kefer to Chapter 3 to recall the effects of concentration on free energy of ATP hydrolysis.)... 

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