Vesicles transport between

Another property of cell membranes in addition to compartmentalization is their ability to fuse. This is important for intracellular vesicle transport between intracellular organelles as well as, for example, for the fusion of enveloped viruses with target cell membranes. 

Lipids are transported between membranes. As indicated above, lipids are often biosynthesized in one intracellular membrane and must be transported to other intracellular compartments for membrane biogenesis. Because lipids are insoluble in water, special mechanisms must exist for the inter- and intracellular transport of membrane lipids. Vesicular trafficking, cytoplasmic transfer-exchange proteins and direct transfer across membrane contacts can transport lipids from one membrane to another. The best understood of such mechanisms is vesicular transport, wherein the lipid molecules are sorted into membrane vesicles that bud out from the donor membrane and travel to and then fuse with the recipient membrane. The well characterized transport of plasma cholesterol into cells via receptor-mediated endocytosis is a useful model of this type of lipid transport. [9, 20]. A brain specific transporter for cholesterol has been identified (see Chapter 5). It is believed that transport of cholesterol from the endoplasmic reticulum to other membranes and of glycolipids from the Golgi bodies to the plasma membrane is mediated by similar mechanisms. The transport of phosphoglycerides is less clearly understood. Recent evidence suggests that net phospholipid movement between subcellular membranes may occur via specialized zones of apposition, as characterized for transfer of PtdSer between mitochondria and the endoplasmic reticulum [21]. 

Other vesicles are surrounded by nonclathrin membrane coats. Some of these originate from caveolae (little caves), which act in endocytosis, exocytosis, and transmembrane signaling.564abc A coatomer complex of eight subunits with molecular masses from 20 to 60 kDa coats vesicles involved in transport between compartments of the Golgi.565-567... 

Protein transport between intracellular compartments is mediated by a mechanism that is well-conserved among all eukaryotes, from yeast to man. The transport mechanism involves carrier vesicles that bud from one organelle and fuse selectively to another. Specialized proteins are required for vesicle transport, docking, and fusion, and they have been generically named SNAREs (an acronym for soluble N-ethylma-leimide-sensitive fusion attachment protein receptor). SNAREs have been divided into those associated with the vesicle (termed v-SNAREs), and those associated with the target (termed t-SNAREs). The key protein, which led to the discovery of SNAREs was NSF, an ATPase found ubiquitously in all cells, and involved in numerous intracellular transport events. The subsequent identification of soluble proteins stably bound to NSF, the so-called SNARE complex, led to the formulation of the SNARE hypothesis, which posits that all intracellular fusion events are mediated by SNAREs (Rothman, 2002). 

The results indicate that the initial rate of transport of PE is rapid and proceeds without a lag (Fig. 8). The transport process is insensitive to metabolic poisons that disrupt vesicle transport and cytoskeletal structure. The rapid transport kinetics occur at rates consistent with a soluble carrier-mediated process or transfer at zones of apposition between membranes. Analysis of the kinetics of the process is complicated since only PE at the outer leaflet of the plasma membrane is measured, and the basal scramblase activity or the leakage of the ATP-dependent aminophospholipid transporter activity within the plasma membrane may be a step required for the lipid to arrive at this location. Despite these complications, the results clearly indicate that the initial rate of arrival of PE at the plasma membrane occurs on a timescale that clearly distinguishes it from well-characterized vesicle transport phenomena, and is independent of processes involved in protein transport to the cell surface. 

Impulse transport between neurons is effected by release of neurotransmitters from the presynaptic neuron into the synaptic cleft where they stimulate their receptors on the membrane of the postsynaptic neuron. Stimulation of the postsynaptic neuron is ended by re-uptake of the neurotransmitter into the presynaptic neuron where it is partly enzymatically inactivated and peu tly stored in presynaptic vesicles. For a minor part the neurotransmitter is taken up in glial cells where it is enzymatically destroyed. 

The question of whether polymers pass between the cells of the epithelia or only through them by vesicle transport is also relevant in the discussion of polymer passage into the intestine lumen and into the bile. Both routes are often assumed in the literature as ways in which polymers can leave the body. 

The data on the relative role of the vesicle transport and diffusion through the intercellular junctions located between the epithelial cells are scarce. The excretion of PVP into the intestine has been described several times. The available information can be briefly summarized as follows The fraction of the (i.v. administered) PVP excreted in the faeces of rats was about 4% of the administered dose after the first day about 7% after three days and about 13% after eight days . Excretion... 

At the outset it is important to note that the transport of material between identical vesicles, as is the case in the vast majority of the studies, occurs mainly via the aqueous phase and not via collisions between vesicles. This was shown both experimentally and theoretically. However Marchi-Artzner et al. ° showed that, when mixing two vesicle populations of low but opposite electrical charge, lipid exchange can occur via contact of the vesicles. In this case, lipid exchange results in the progressive neutralization of the electrical charge of the vesicles, without fusion of the vesicle inner compartments. Most of the studies reviewed below consider transport between identical vesicles. 

Transport of membrane lipids from the site of synthesis to the target membranes has been postulated to be mediated by membrane vesicles, by lipid transport proteins and/or to occur at contact sites between membranes [1-3]. Vesicular-mediated lipid transport between plant membranes has been reconstituted in cell-free systems. The results suggest that transport of lipids from endoplasmic reticulum (ER) to the Golgi apparatus [4,5] or to the chloroplast envelope (Sandelius and Rantfors, unpublished) and from the envelope to the thylakoid [6] is metabolically regulated, as shown by temperature dependence and requirement of and/or stimulation by ATP and cytosol or stroma. 

The spectmm of protein functions in a biological organism is manifold. Proteins are involved in almost all cell processes. Ion channels and nanopores formed by membrane proteins control ion and water flow into and out of the cell [4]. Figure 1.3 shows the atomic stmcture of the membrane protein aquaporine, a pore embedded in the cell membrane that is permeable for water molecules. The efficiency is extreme. Up to 3 billion water molecules can msh through this pore per second [5,6]. Other cell proteins like actin, for example, are responsible for the mechanical stability of the cell backbone. Actin polymerizes to filaments and these filaments can form stable networks. Besides cell stability, these networks also enable transport processes along these tracks, e.g., vesicle transport mediated by myosin proteins. The interplay between actin and myosin is also important for the ability of muscle tissue to contract. Biochemical reactions are catalyzed... 

FIGURE 17.8 (a) Rapid axonal transport along microtnbnles permits the exchange of material between the synaptic terminal and the body of the nerve cell, (b) Vesicles, mnltivesicn-lar bodies, and mitochondria are carried throngh the axon by this mechanism. 

The presently known mammalian AQP0-AQP12 have been localized in tissues involved in fluid transport as well as in nonfluid-transporting tissues (Table 1). Most AQPs are constitutively present in the plasma membrane, whereas some water channels can be triggered to shuttle between intracellular vesicles and the plasma membrane [2]. 

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