Plasma membrane of mammalian cells

The most common sterol in membranes is cholesterol (Chapter 14), which resides mainly in the plasma membranes of mammalian cells but can also be found in lesser quantities in mitochondria, Golgi complexes, and nuclear membranes. Cholesterol intercalates among the phospholipids of the membrane, with its hydroxyl group at the aqueous interface and the remainder of the molecule within the leaflet. Its effect on the fluidity of membranes is discussed subsequently. 

Since in mammalian species metals first need to be assimilated from dietary sources in the intestinal tract and subsequently transported to the cells of the different organs of the body through the bloodstream, we will restrict ourselves in this section to the transport of metal ions across the enterocytes of the upper part of the small intestine (essentially the duodenum), where essentially all of the uptake of dietary constituents, whether they be metal ions, carbohydrates, fats, amino acids, vitamins, etc., takes place. We will then briefly review the mechanisms by which metal ions are transported across the plasma membrane of mammalian cells and enter the cytoplasm, as we did for bacteria, fungi and plants. The specific molecules involved in extracellular metal ion transport in the circulation will be dealt with in Chapter 8. 

Nickel W (2005) Unconventional secretory routes direct protein export across the plasma membrane of mammalian cells. Traffic 6 607-614... 

If we focus on the mammalian cell, we have the plasma membrane, which encompasses the cell and separates what is inside from what is outside. We also find the membranes that isolate the nucleus, the mitochondria, the lysosomes, and other intracellular organelles from the cytoplasm. AU of these membranes have their own peculiarities and distinctions. However, it is not my purpose to make a catalog of known membrane types but to provide insights into the structural and functional features that are common to many membrane types. Since we need something specific to talk about, let s focus on the plasma membrane of mammalian cells. A schematic view of such a membrane is provided in figure 19.1. 

If bound first by albumin, heme circulates until it is transferred to hemopexin (52). In vitro in the absence of hemopexin, nonspecific cellular uptake of heme by diffusion is facile (55), but as expected, the presence of hemopexin greatly slows uptake (54), since receptor-mediated uptake is necessarily slower and of lower capacity than diffusion-limited uptake. There is currently no evidence that either receptors for albumin or membrane transporters for heme, like those in prokaryotes, are present in the plasma membrane of mammalian cells, although such transport proteins may be present in the membranes of organelles. 

An H+ electrochemical gradient (ApH+) provides the energy required for active transport of all classical neurotransmitters into synaptic vesicles. The Mg2+-dependent vacuolar-type H+-ATPase (V-ATPase) that produces this gradient resides on internal membranes of the secretory pathway, in particular endosomes and lysosomes (vacuole in yeast) as well as secretory vesicles (Figure 3). In terms of both structure and function, this pump resembles the F-type ATPases of bacteria, mitochondria and chloroplasts, and differs from the P-type ATPases expressed at the plasma membrane of mammalian cells (e.g., the Na+/K+-, gastric H+/K+-and muscle Ca2+-ATPases) (Forgac, 1989 Nelson, 1992). The vacuolar and F0F1... 

The Na-K ATPase, in the plasma membrane of mammalian cells, is inhibited when ouabain binds to the a subunit that is phosphorylated during catalysis.21 372 Unlike HGPRT" and TK"/", the ouabain-resistant phenotype (assigned to chromosome 3 in the mouse)218 is dominant, stable, and characterized by a reduced uptake of 86Rb and 1 2K in the presence of ouabain and by reduced binding of ouabain to the plasma membrane.21 Ouabain resistance can be induced... 

Pralle, A., Keller, P., Florin, E.L., Simons, K., Horber, J.K.H. Sphingolipid-cholesterol rafts diffuse as small entities in the plasma membrane of mammalian cells. J Cell Biol 148 (2000)... 

Oehlke, J., Beyermann, M., Wiesner, B., et al. (1997) Evidence for extensive and non-specific translocation of oligopeptides across plasma membranes of mammalian cells. Biochim. Biophys. Acta 1330, 50-60. 

Synthetic mimics of cell-surface receptors have been constructed using plasma membrane anchors derived from N -alkyl-3fi-cholesterylamine and related compounds (14). Synthetic receptors comprising protein and other binding motifs linked to this membrane anchor become incorporated rapidly into plasma membranes of mammalian cells. By constimtively cycling between the plasma membrane and the endosomes, cells treated with these compounds gain the capacity to endocytose cell-impermeable hgands. For example, the synthetic Fc receptor shown in Fig. 4 enables human cells that lack Fc receptors... 

Copper uptake across the gastrointestinal tract is poorly understood — most probably utihsing the divalent cation transporter DMTl. At the cellular level, Cu is imported across the plasma membrane of mammalian cells as Cu, by members of the CTR family. The CTR family of proteins have been found in yeast and plants, as we saw, but also in humans and other mammals. They contain several methionine-rich motifs at their N-terminus, and conserved cysteine and histidine residues at their C-terminus. Unusually, CTR proteins can mediate the uptake of platinum anticancer drugs into mammalian cells (see Chapter 22). 

Cholesterol and its derivatives constitute the third important class of membrane lipids, the steroids. The basic structure of steroids is a four-ring hydrocarbon. Cholesterol, the major steroidal constituent of animal tissues, has a hydroxyl substituent on one ring (Figure 5-5c). Although cholesterol is almost entirely hydrocarbon in composition, it is amphlpathlc because its hydroxyl group can interact with water. Cholesterol is especially abundant in the plasma membranes of mammalian cells but is absent from most prokaryotic cells. As much as 30-50 percent of the lipids in plant plasma membranes consist of certain steroids unique to plants. 

Bevers, E M, Comfurius, P, Dekkers, D W C, and Zwaal, R F A, Lipid translocation across the plasma membrane of mammalian cells, Biochim. Biophys. Acta - Molecular and Cell Biology of Lipids 1439 (1999) 317-330. 

Nucleotidases possessing 3 - and 5 -hydrolase activities are present on the surface of L. donovani and L. mexicana (32). Cell surface 5 -nucleotidases are commonly present on the plasma membrane of mammalian cells and are believed to be involved in purine... 

Cell-penetrating peptides (CPPs), Trojan horse peptides, protein transduction domains, peptides of different stmctural classes that are capable to cross the plasma membranes of mammalian cells in an... 

Cholesterol does not form micelles because it is not sufficiently amphiphilic (even though it does have an —OH group) and its flat, rigid, fused-ring structure gives a solid rather than a liquid hydrocarbon phase at physiological temperatures. Such fluidity is required for micelle formation. However, cholesterol can form mixed micelles with amphiphilic lipids, and it enters monolayers as well where it constitutes -25% of the mass of the lipid bilayer in the plasma membranes of mammalian cells. 

In a review, a comparison has been made of the specific combining sites of a number of lectins and those of antibodies to blood-group substances. A comprehensive review of both plant and animal lectins has been published. The application of lectins for the purification and characterization of enzymes and other proteins has been reviewed in order to define some of the variables that affect the binding of glycoproteins to lectins. The role of the oligosaccharides of cell-wall surface glycoproteins in variants of plasma membranes of mammalian cells that are resistant to cytotoxic lectins has been assessed. ... 

Doyle, D., and Baumann, H., 1979, Turnover of the plasma membrane of mammalian cells. Life Sci. 24 951. 

GLUTl Uniporter protein that laciKtates the transport of glucose across the plasma membrane of mammalian cells Widely distributed in fetal tissues Adult Red blood cells EndoUielial cells Rabbit anti-GLUTl, Sigma, St Louis, MO... 

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