Plasma membrane mediated transport

The vesicular monoamine transporters (VMATs) were identified in a screen for genes that confer resistance to the parkinsonian neurotoxin MPP+ [2]. The resistance apparently results from sequestration of the toxin inside vesicles, away from its primary site of action in mitochondria. In addition to recognizing MPP+, the transporter s mediate the uptake of dopamine, ser otonin, epinephrine, and norepinephrine by neurons and endocrine cells. Structurally, the VMATs show no relationship to plasma membrane monoamine transporters. 

VMATs are not inhibited by drugs such as cocaine, tricyclic antidqnessants and selective serotonin reuptake inhibitors that affect plasma membrane monoamine transport. Amphetamines have relatively selective effects on monoaminergic cells due to selective uptake by plasma membrane monoamine transporters, but their effect appears to be mediated by their ability as weak bases to reduce ApH, the driving force for vesicular monoamine transport that leads to efflux of the vesicular contents into the cytoplasm. 

Figure 4.4 Comparison of oxidase-dependent iron transport in mammals and yeast. In mammals, the plasma glycoprotein cerulpolasmin mediates iron oxidation, facilitating iron export from the cells and delivery to other tissues throughout the body. In yeast, Fet3p, an integral membrane protein mediates iron oxidation, resulting in plasma membrane iron transport through the permease Ftrlp. Reprinted from Askwith and Kaplan, 1998. Copyright (1998), with permission from Elsevier Science.

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... 

SODIUM-DEPENDENT GLUTAMINE TRANSPORTERS IN PLASMA MEMBRANES MEDIATE THE TRANSFER OF GLUTAMINE FROM ASTROCYTES TO NEURONS 287... 

Torres GE, Gainetdinov RR, Caron MG (2003a) Plasma membrane monoamine transporters structure, regulation and function. Nat Rev Neurosci 4 13-25 Vaughan RA, Huff RA, Uhl GR, Kuhar MJ (1997) Protein kinase C-mediated phosphorylation and functional regulation of dopamine transporters in striatal synaptosomes. J Biol Chem 272 15541-15546... 

The flux of a substrate (rate of transport) across the plasma membrane via transporter-mediated processes is characterized by saturabUity. The relationship between the flux v and substrate concentration C in a transporter-mediated process is analogous to the rate of product formed by an enzyme and the concentration of substrate. The maximum transport rate is proportional to the density of transporters on the plasma membrane, and the represents the substrate concentration at which the flux is half maximal. When C is small compared with the K, the flux is increased in proportion to the substrate concentration (roughly linearly). If C is large compared with the K value, the flux approaches the maximal value (V ). The and V values can be deter-... 

Fig. 10.16. Lysosomes in receptor-mediated endocytosis via clathrin-coated pits. 1 Endo-cytotic vesicles fuse to form early endosomes. 2 Vesicle contents are sorted, and receptors, clathrin, and lipids are sent back to the plasma membrane. 3 Transport vesicles from the trans-Golgi carry lysosomal hydrolases to the late endosome. 4 Lysosomes containing concentrated hydrolases digest proteins and other components acquired from endocytotic vesicles.

Horemans, N., Asard, H., and Caubergs, R. J., 1994, The role of ascorbate free radical as an electron acceptor to cytochrome -mediated trans-plasma membrane electron transport in higher plants. Plant Physiol. 104 1455-1458. 

DMTl functions in the transport of ferrous iron (Fe II) and certain nonessential divalent ions, e.g., lead and cadmium, across the plasma membrane and out of the endosomal compartment in a pH-dependent fashion. In the mammalian GI tract, DMTl mediates apical Fe uptake into duodenal entero-cytes lining the small intestine and also serves a general cellular role in tandem with the transferrin receptor (TFR) by using Fe-loaded diferric transferrin at the plasma membrane. It transports the iron via the endosome into cytosol. 

Because dopamine itself is also a Dj-agonist, one might assume that it would exhibit quinpirole-like effects on quantal release however, incubation in 50 jM dopamine serves to increase, rather than decrease, the quantal size of individual release events [56]. Becanse dopamine is a universal agonist at all dopamine receptor snbtypes, it also activates the Dj receptor subtype present in PC 12 cells and serves as a snbstrate for the plasma membrane dopamine transporter and for the vesicnlar monoamine transporter, VMATl. Thus, incubation in dopamine does not provide a straightforward approach to the analysis of receptor-mediated modnlations of qnantal size. 

Some investigators have employed the enhancement of vascular tone in vivo after treatment with these drugs to inhibit amine reuptake where the flavonoids act as antagonists of plasma membrane amine transporters [104]. The vasodilatory mechanism of flavonoids seems to be mediated by the inhibition of protein kinase C [105]. Oilier recent studies on the potential vasorelaxant, antioxidant, and cyclic nucleotide phosphodiesterase (PDE) inhibitory effects of the citrus-fruit flavonoids nar-ingenin and hesperetin in intact rat aortic rings have shown that their vasorelaxant effects were mediated by the inhibition of different PDE isoenz5Tnes [106,107]. 

One primary neurochemical mode of action of MDMA involves an indirectly mediated release of monoamines via reversed plasma membrane monoamine transport function and disruption of vesicular storage. Increased 5-HT release appears to be the dominating feature and DA, NA and acetylcholine release are also observed to be involved, although to a lesser degree. Additional mechanisms include inhibition of tryptophan hydroxylase and MAO-A, as well as involvement of S-ffTjA receptors. 

Biochemically, most quaternary ammonium compounds function as receptor-specific mediators. Because of their hydrophilic nature, small molecule quaternaries caimot penetrate the alkyl region of bdayer membranes and must activate receptors located at the cell surface. Quaternary ammonium compounds also function biochemically as messengers, which are generated at the inner surface of a plasma membrane or in a cytoplasm in response to a signal. They may also be transferred through the membrane by an active transport system. 

MTs extend from the centrosome throughout the cytoplasm to the plasma membrane, where they are stabilized by caps. Sliding along the MTs, kinesin and dynein motors transport their cargoes between the center and the periphery of the cell. MTs present in the axons of neur ons are extended not only by addition of heterodimers to the plus ends but also by use of short MTs that initiate in the centrosome. Their axonal transport is mediated by dynein motors that are passively moved along actin filaments. Once formed in the axon, MTs serve as tracks for the fast axonal transport, i.e. the movement of membranous organelles and membrane proteins to the nerve ending. 

The insulin receptor is a transmembrane receptor tyrosine kinase located in the plasma membrane of insulin-sensitive cells (e.g., adipocytes, myocytes, hepatocytes). It mediates the effect of insulin on specific cellular responses (e.g., glucose transport, glycogen synthesis, lipid synthesis, protein synthesis). 

Fat Increased glucose transport GLUT4-translocation PI 3-kinase/Akt mediated translocation of GLUT4 into the plasma membrane. Potential involvement of atypical forms of protein kinase C (PKC and A)... 

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