alexa The role of zinc ions in reverse transport mediated by monoamine transporters.
Biochemistry

Biochemistry

Journal of Membrane Science & Technology

Author(s): Scholze P, Nrregaard L, Singer EA, Freissmuth M, Gether U,

Abstract Share this page

Abstract The human dopamine transporter (hDAT) contains an endogenous high affinity Zn2+ binding site with three coordinating residues on its extracellular face (His193, His375, and Glu396). Upon binding to this site, Zn2+ causes inhibition of [3H]1-methyl-4-phenylpyridinium ([3H]MPP+) uptake. We investigated the effect of Zn2+ on outward transport by superfusing hDAT-expressing HEK-293 cells preloaded with [3H]MPP+. Although Zn2+ inhibited uptake, Zn2+ facilitated [3H]MPP+ release induced by amphetamine, MPP+, or K+-induced depolarization specifically at hDAT but not at the human serotonin and the norepinephrine transporter (hNET). Mutation of the Zn2+ coordinating residue His(193) to Lys (the corresponding residue in hNET) eliminated the effect of Zn2+ on efflux. Conversely, the reciprocal mutation (K189H) conferred Zn2+ sensitivity to hNET. The intracellular [3H]MPP+ concentration was varied to generate saturation isotherms; these showed that Zn2+ increased V(max) for efflux (rather than K(M-Efflux-intracellular)). Thus, blockage of inward transport by Zn2+ is not due to a simple inhibition of the transporter turnover rate. The observations provide evidence against the model of facilitated exchange-diffusion and support the concept that inward and outward transport represent discrete operational modes of the transporter. In addition, they indicate a physiological role of Zn2+, because Zn2+ also facilitated transport reversal of DAT in rat striatal slices. This article was published in J Biol Chem and referenced in Journal of Membrane Science & Technology

Relevant Expert PPTs

Relevant Speaker PPTs

Recommended Conferences

  • 1st World Congress on Nano Science and Nano Technology
    July 10-11, 2017 Jakarta, Indonesia
  • Annual Meeting on Separation Techniques
    July 12-14, 2017 bangkok, Thailand
  • Biotechnology Congress
    July 17-19, 2017 Kualalumpur, Malaysia
  • 2nd International Conference and Expo on Water Microbiology & Novel Technologies
    (10 Plenary Forums 3 days 1 Event)
    August 28-30, 2017, Philadelphia, USA

Relevant Topics

Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

 
© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version
adwords