Structure and function of polyamine transport systems and NMDA receptors

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1.Polyamine transport in Saccharomyces cerevisiae was studied. (1)TPO1, located on the plasma membrane, catalyzed the excretion of polyamines. The transport activity of TPO1 was enhanced through phosphorylation at Ser^<19> protein kinase C and at Thr^<52> by casein kinase 1. Sorting of TPO1 from the endoplasmic reticulum to the plasma membrane was enhanced through phosphorylation at Ser^<342> by cAMP dependent protein kinases 1 and 2. (2)TPO5 encoded by YKL174c catalyzed the excretion of putrescine and spermidine, and it was localized on Golgi or post-Golgi secretory vesicles, suggesting that secretory and endocytic pathways, are involved in the excretion of polyamines by TPO5. (3)We found that urea transporter DUR3 and S-adenosylmethionine transporter SAM3, located on plasma membrane, catalyze polyamine uptake preferentially, and that the expression of both mRNAs were repressed by the presence of polyamines in medium.2.NMDA (N-methyl-D-aspartate) receptor is a subtype of glutamate rec … More eptors and involved in the plasticity of central nerves system. The effects of various anthraquinone polyamines (AQP) were studied at NMDA receptors expressed in Xenopus laevis oocytes. All AQP derivatives inhibited responses of NR1/NR2 receptors in oocytes voltage-clamped at -70 mV. The block was strongly voltage-dependent. AQ spermidine (AQ34) inhibited responses of NR1/NR2 receptors but did not inhibit responses of AMPA receptors indicating that AQ34 is preferential NMDA antagonists. Results of experiments using mutant NR1 and NR2 subunits identified residues that influence block by AQ34. These residues are located in the outer vestibule at the selectivity filter/narrowest constriction of the channel and in the inner vestibule below the level of the selectivity filter. Regulatory domain (R-domain) proteins of NMDA receptor subunits were purified and the properties of the proteins were determined. It was suggested that binding sites of spermine and ifenprodil on R-domain proteins are different each other. Less