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

John P. Norman; Seth W. Perry; Holly M. Reynolds; Michelle Kiebala; Karen L. De Mesy Bentley; Margarita Trejo; David J. Volsky; Sanjay B. Maggirwar; Stephen Dewhurst; Eliezer Masliah; Harris A. Gelbard

doi:10.1371/journal.pone.0003731

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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

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

John P. Norman,
Seth W. Perry,
Holly M. Reynolds,
Michelle Kiebala,
Karen L. De Mesy Bentley,
Margarita Trejo,
David J. Volsky,
Sanjay B. Maggirwar,
Stephen Dewhurst,
Eliezer Masliah

Published: November 14, 2008
https://doi.org/10.1371/journal.pone.0003731

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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!

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

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

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

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