Vesicles membrane transporters

In order to characterize lipid vesicle membrane transport properties further, we have begun to study the transport of other molecules and test whether correlations might also exist with mechanical compressibility and water permeability. Here, although some data exists for black lipid membranes [33], little attention has so far been paid to the transport of small molecules and ions for giant vesicular membranes (i.e, free of solvent and boundary-support effects) [87] and none using the micropipet technique on single vesicles. The new series of transport studies considers first urea, which is both a water-soluble and membrane-soluble molecule. 

COPII vesicles are transport intermediates from the endoplasmic reticulum. The process is driven by recruitment of the soluble proteins that form the coat structure called COPII from the cytoplasm to the membrane. 

In addition to secretory cells, many non-secretory cells are capable of regulating exocytotic fusion of transport vesicles that are derived from endosomal precursors. For instance, vesicles enriched in plasma membrane transport proteins are incorporated in a regulated manner in order to alter metabolite fluxes. Examples include the glucose transporter GLUT-4 in muscle and fat tissues, a key element in the control of... 

Once the proteins have passed the quality control system of the early secretory pathway, they are transported in vesicles via the individual compartments of the Golgi apparatus to the plasma membrane. Soluble proteins are transported in the vesicle lumen, membrane proteins are integrated in the vesicle membrane. The transport to the cell surface is the default pathway for secretory and membrane proteins. Proteins may also become part of one of the intracellular compartments along the secretory pathway, but only if they contain specific retention signals. 

Vesicles are transport containers that are formed upon recruitment of coat proteins from a donor membrane that fuse with an acceptor membrane. 

The exocytotic release of neurotransmitters from synaptic vesicles underlies most information processing by the brain. Since classical neurotransmitters including monoamines, acetylcholine, GABA, and glutamate are synthesized in the cytoplasm, a mechanism is required for their accumulation in synaptic vesicles. Vesicular transporters are multitransmembrane domain proteins that mediate this process by coupling the movement of neurotransmitters to the proton electrochemical gradient across the vesicle membrane. 

Synaptic vesicles isolated from brain exhibit four distinct vesicular neurotransmitter transport activities one for monoamines, a second for acetylcholine, a third for the inhibitory neurotransmitters GABA and glycine, and a fourth for glutamate [1], Unlike Na+-dependent plasma membrane transporters, the vesicular activities couple to a proton electrochemical gradient (A. lh+) across the vesicle membrane generated by the vacuolar H+-ATPase ( vacuolar type proton translocating ATPase). Although all of the vesicular transport systems rely on ApH+, the relative dependence on the chemical and electrical components varies (Fig. 1). The... 

As described above, because MAO is bound to mitochondrial outer membranes, MAOIs first increase the concentration of monoamines in the neuronal cytosol, followed by a secondary increase in the vesicle-bound transmitter. The enlarged vesicular pool will increase exocytotic release of transmitter, while an increase in cytoplasmic monoamines will both reduce carrier-mediated removal of transmitter from the synapse (because the favourable concentration gradient is reduced) and could even lead to net export of transmitter by the membrane transporter. That MAOIs increase the concentration of extracellular monoamines has been confirmed using intracranial microdialysis (Ferrer and Artigas 1994). 

The main problems with early, irreversible MAOIs were adverse interactions with other drugs (notably sympathomimetics, such as ephedrine, phenylpropanolamine and tricyclic antidepressants) and the infamous "cheese reaction". The cheese reaction is a consequence of accumulation of the dietary and trace amine, tyramine, in noradrenergic neurons when MAO is inhibited. Tyramine, which is found in cheese and certain other foods (particularly fermented food products and dried meats), is normally metabolised by MAO in the gut wall and liver and so little ever reaches the systemic circulation. MAOIs, by inactivating this enzymic shield, enable tyramine to reach the bloodstream and eventually to be taken up by the monoamine transporters on serotonergic and noradrenergic neurons. Fike amphetamine, tyramine reduces the pH gradient across the vesicle membrane which, in turn, causes the vesicular transporter to fail. Transmitter that leaks out of the vesicles into the neuronal cytosol cannot be metabolised because... 

Garcia Ruiz, C., Fernandez Checa, J. and Kaplowitz, N. (1992). Bidirectional mechanism of plasma membrane transport of reduced glutathione in intact rat hepatocytes and membrane vesicles. J. Biol. Chem. 267, 2256-2264. 

Packaging neurotransmitters into presynaptic vesicles is mediated by proton-coupled antiporters. As discussed above, Golgi-derived membranes, including presynaptic vesicle membranes, contain V-type primary transporters that pump protons into the lumen of these membranes and vesicles. 

Most transport vesicles bud off as coated vesicles, with a unique set of proteins decorating their cytosolic surface 141 GTP-binding proteins, such as the small monomeric GTPases and heterotrimeric GTPases (G proteins) facilitate membrane transport 142 SNARE proteins and Rabs control recognition of specific target membranes 143... 

Clathrin-coated vesicles mediate transport from the Golgi apparatus to endosomes, and from the plasma membrane to endosomes. A multi-subunit protein, clath-rin, constitutes the major protein of this vesicle type (see Ch. 2). Clathrin is composed of three large and three small polypeptide chains, which assemble to form a triskelion (Fig. 9-2). Regulatory mechanisms control the assembly and formation of a convex, polyhexa-pentagonal basketlike structure by these triskelions [5], This structure is responsible for the formation of coated pits on the cytosolic face of plasma membranes. 

All eukaryotic cells possess an unspecialized exocytic pathway known as the constitutive secretion. Vesicle membranes in this pathway fuse with the plasma membrane without any extracellular signal. As noted above, proteins destined for the secretory pathway are sorted at the level of the TGN. Proteins to be transported to the plasma membrane are directed into a constitutive secretory pathway. 

Transport proteins (channels) for chloride and zinc Vacuolar proton pump Components of synaptic vesicles to mediate the chloride flux for glutamate uptake and zinc uptake in most synaptic vesicles. Zinc transporter is homologous to endosomal and plasma membrane zinc transporters chloride transporters remain to be identified. Protein complex of more than 12 subunits. Constitutes the largest component of synaptic vesicles and establishes... 

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