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Research Article

HIV-1 Tat Activates Neuronal Ryanodine Receptors with Rapid Induction of the Unfolded Protein Response and Mitochondrial Hyperpolarization

  • John P. Norman,

    Affiliations: Center for Neural Development and Disease, the University of Rochester School of Medicine and Dentistry, Rochester, New York, United States of America, Department of Neurology (Child Neurology Division), the University of Rochester School of Medicine and Dentistry, Rochester, New York, United States of America

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  • Seth W. Perry,

    Affiliations: Center for Neural Development and Disease, the University of Rochester School of Medicine and Dentistry, Rochester, New York, United States of America, Department of Neurology (Child Neurology Division), the University of Rochester School of Medicine and Dentistry, Rochester, New York, United States of America

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  • Holly M. Reynolds,

    Affiliations: Center for Neural Development and Disease, the University of Rochester School of Medicine and Dentistry, Rochester, New York, United States of America, Department of Neurology (Child Neurology Division), the University of Rochester School of Medicine and Dentistry, Rochester, New York, United States of America

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  • Michelle Kiebala,

    Affiliation: Department of Microbiology and Immunology, the University of Rochester School of Medicine and Dentistry, Rochester, New York, United States of America

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  • Karen L. De Mesy Bentley,

    Affiliation: Department of Laboratory Medicine and Pathology, the University of Rochester School of Medicine and Dentistry, Rochester, New York, United States of America

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  • Margarita Trejo,

    Affiliation: Department of Neurosciences and Department of Pathology, School of Medicine, University of California San Diego, La Jolla, California, United States of America

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  • David J. Volsky,

    Affiliation: Molecular Virology Division, St. Lukes-Roosevelt Hospital Center, Columbia University, New York, New York, United States of America

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  • Sanjay B. Maggirwar,

    Affiliation: Department of Microbiology and Immunology, the University of Rochester School of Medicine and Dentistry, Rochester, New York, United States of America

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  • Stephen Dewhurst,

    Affiliation: Department of Microbiology and Immunology, the University of Rochester School of Medicine and Dentistry, Rochester, New York, United States of America

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  • Eliezer Masliah,

    Affiliation: Department of Neurosciences and Department of Pathology, School of Medicine, University of California San Diego, La Jolla, California, United States of America

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  • Harris A. Gelbard mail

    harris_gelbard@urmc.rochester.edu

    Affiliations: Center for Neural Development and Disease, the University of Rochester School of Medicine and Dentistry, Rochester, New York, United States of America, Department of Neurology (Child Neurology Division), the University of Rochester School of Medicine and Dentistry, Rochester, New York, United States of America, Department of Microbiology and Immunology, the University of Rochester School of Medicine and Dentistry, Rochester, New York, United States of America

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  • Published: November 14, 2008
  • DOI: 10.1371/journal.pone.0003731

Reader Comments (2)

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HIV-1 Tat Activates Neuronal Ryanodine Receptors........

Posted by hegendel on 16 Nov 2008 at 23:54 GMT

For a number of years the relevance of HIV-1 Tat for neuroAIDS has been subject to vigorous discussion. This and prior works by the Gelbard group have developed a pathway to help shed light on this issue. The investigators found that neuronal mitochondrial hyperpolarization occurs in response to Tat and affects the ability of the neuron to buffer calcium and sustain energy production for normal synaptic communication. In the current report they demonstrate that Tat induces rapid loss of ER calcium mediated by the ryanodine receptor (RyR). Most importantly the investigators were able to show clinical links to their biologic findings. Exciting stuff!