ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2011
The human immunodeficiency virus coat protein gp120 promotes forward trafficking and surface clustering of NMDA receptors in membrane microdomains.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 48 citations in OpenAlex.
- HIV-1 gp120 Induces Nociceptive Hypersensitivity via α2δ-1-Bound NMDA Receptors at Primary Afferent→Excitatory Neuron Synapses.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Review
- NMDA-Type Glutamate Receptor Activation Promotes Ischemic Arrhythmias by Targeting the AKT1-TBX3-Nav1.5 Axis.Acta physiologica (Oxford, England) · 2025Article
- HIV-1 gp120 protein promotes HAND through the calcineurin pathway activation.Mitochondrion · 2023Article
- Neutral sphingomyelinase 2 inhibition attenuates extracellular vesicle release and improves neurobehavioral deficits in murine HIV.Neurobiology of disease · 2022Article
- HIV and FIV glycoproteins increase cellular tau pathology via cGMP-dependent kinase II activation.Journal of cell science · 2022Article
- Article
- Unbiased Metabolomics Links Fatty Acid Pathways to Psychiatric Symptoms in People Living with HIV.Journal of clinical medicine · 2021Article
- HMGB1 mediates cognitive impairment caused by the NLRP3 inflammasome in the late stage of traumatic brain injury.Journal of neuroinflammation · 2021Article
- Mechanisms of neuronal dysfunction in HIV-associated neurocognitive disorders.Cellular and molecular life sciences : CMLS · 2021Review
- Novel Therapeutic Approach for Excitatory/Inhibitory Imbalance in Neurodevelopmental and Neurodegenerative Diseases.Annual review of pharmacology and toxicology · 2021Review
- HIV-Associated Neurotoxicity: The Interplay of Host and Viral Proteins.Mediators of inflammation · 2021Review
- Article
- HIV influences microtubule associated protein-2: potential marker of HIV-associated neurocognitive disorders.AIDS (London, England) · 2020Article
- The Glutamate System as a Crucial Regulator of CNS Toxicity and Survival of HIV Reservoirs.Frontiers in cellular and infection microbiology · 2020Review
- Scaling Synapses in the Presence of HIV.Neurochemical research · 2019Review
- HIV induces synaptic hyperexcitation via cGMP-dependent protein kinase II activation in the FIV infection model.PLoS biology · 2018Article
- HIV Associated Neurodegenerative Disorders: A New Perspective on the Role of Lipid Rafts in Gp120-Mediated Neurotoxicity.Current HIV research · 2018Review
- The lipid raft-dwelling protein US9 can be manipulated to target APP compartmentalization, APP processing, and neurodegenerative disease pathogenesis.Scientific reports · 2017Article
- Human Immunodeficiency Virus Promotes Mitochondrial Toxicity.Neurotoxicity research · 2017Review
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Infection by the human immunodeficiency virus (HIV) can result in debilitating neurological syndromes collectively known as HIV-associated neurocognitive disorders. Although the HIV coat protein gp120 has been identified as a potent neurotoxin that enhances NMDA receptor function, the exact mechanisms for this effect are not known. Here we provide evidence that gp120 activates two separate signaling pathways that converge to enhance NMDA-evoked calcium flux by clustering NMDA receptors in modified membrane microdomains. gp120 enlarged and stabilized the structure of lipid microdomains on dendrites by mechanisms that involved a redox-regulated translocation of a sphingomyelin hydrolase (neutral sphingomyelinase-2) to the plasma membrane. A concurrent pathway was activated that accelerated the forward traffic of NMDA receptors by a PKA-dependent phosphorylation of the NR1 C-terminal serine 897 (masks an ER retention signal), followed by a PKC-dependent phosphorylation of serine 896 (important for surface expression). NMDA receptors were preferentially targeted to synapses and clustered in modified membrane microdomains. In these conditions, NMDA receptors were unable to laterally disperse and did not internalize, even in response to strong agonist induction. Focal NMDA-evoked calcium bursts were enhanced by threefold in these regions. Inhibiting membrane modification or NR1 phosphorylation prevented gp120 from accelerating the surface localization of NMDA receptors. Disrupting the structure of membrane microdomains after gp120 treatments restored the ability of NMDA receptors to disperse and internalize. These findings demonstrate that gp120 contributes to synaptic dysfunction in the setting of HIV infection by interfering with NMDA receptor trafficking.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.