Human immunodeficiency virus type 1 Tat protein directly activates neuronal N-methyl-D-aspartate receptors at an allosteric zinc-sensitive site

L. Song, A. Nath, J. D. Geiger, A. Moore, Shawn Hochman

Research output: Contribution to journalArticlepeer-review

72 Scopus citations

Abstract

The human immunodeficiency virus type 1 (HIV-1) regulatory protein Tat is neurotoxic and may be involved in the neuropathogenesis of HIV-1 dementia, in part via N-methyl-D-aspartate (NMDA) receptor activation. Here, in acutely isolated rat hippocampal neurons, Tat evoked inward currents reversing near 0 mV, with a negative slope conductance region characteristic of NMDA receptor activation. Although the NMDA receptor antagonist ketamine blocked Tat's actions, competitive glutamate- and glycine-binding site antagonists were ineffective (AP-5 and 5,7-dichlorokynurenate, respectively). Evidence for Tat acting at a distinct modulatory site on the NR1 subunit of NMDA receptors was provided by findings that 1 μM Zn2+ abolished Tat-evoked responses in all neurons tested. Thus, Tat appears to excite neurons via direct activation of the NMDA receptor at an allosteric Zn2+-sensitive site.

Original languageEnglish (US)
Pages (from-to)399-403
Number of pages5
JournalJournal of neurovirology
Volume9
Issue number3
DOIs
StatePublished - Jun 2003

Keywords

  • AIDS
  • Excitatory amino acid receptors
  • HIV-1
  • NMDA
  • Zinc

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience
  • Virology

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