Journal article
Defining the molecular mechanisms of HIV-1 Tat secretion: PtdIns(4,5)P-2 at the epicenter
Traffic (Copenhagen, Denmark), v 19(9), pp 655-665
01 Sep 2018
PMID: 29708629
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The human immunodeficiency virus type 1 (HIV-1) transactivator of transcription (Tat) protein functions both intracellularly and extracellularly. Intracellularly, the main function is to enhance transcription of the viral promoter. However, this process only requires a small amount of intracellular Tat. The majority of Tat is secreted through an unconventional mechanism by binding to phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P-2), a phospholipid in the inner leaflet of the plasma membrane that is required for secretion. This interaction is mediated by the basic domain of Tat (residues 48-57) and a conserved tryptophan (residue 11). After binding to PtdIns(4,5)P-2, Tat secretion diverges into multiple pathways, which we categorized as oligomerization-mediated pore formation, spontaneous translocation and incorporation into exosomes. Extracellular Tat has been shown to be neurotoxic and toxic to other cells of the central nervous system (CNS) and periphery, able to recruit immune cells to the CNS and cerebrospinal fluid, and alter the gene expression and morphology of uninfected cells. The effects of extracellular Tat have been examined in HIV-1-associated neurocognitive disorders (HAND); however, only a small number of studies have focused on the mechanisms underlying Tat secretion. In this review, the molecular mechanisms of Tat secretion will be examined in a variety of biologically relevant cell types.
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Details
- Title
- Defining the molecular mechanisms of HIV-1 Tat secretion: PtdIns(4,5)P-2 at the epicenter
- Creators
- Anthony R. Mele - Drexel UniversityJamie Marino - Drexel UniversityKenneth Chen - Department of Biology, University of the Sciences, Philadelphia, Pennsylvania.Vanessa Pirrone - Drexel UniversityChris Janetopoulos - Department of Biology, University of the Sciences, Philadelphia, Pennsylvania.Brian Wigdahl - Drexel UniversityZachary Klase - Department of Biology, University of the Sciences, Philadelphia, Pennsylvania.Michael R. Nonnemacher - Drexel University
- Publication Details
- Traffic (Copenhagen, Denmark), v 19(9), pp 655-665
- Publisher
- Wiley
- Number of pages
- 11
- Grant note
- DP2DA044550 / NATIONAL INSTITUTE ON DRUG ABUSE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Drug Abuse (NIDA); European Commission P30 MH092177 T32 MH079785 / National Institute of Mental Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Mental Health (NIMH) R01 NS089435 / National Institute of Neurological Disorders and Stroke; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS) T32MH079785 / NATIONAL INSTITUTE OF MENTAL HEALTH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Mental Health (NIMH) R01NS089435 / NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology; Digital Media; Pharmacology and Physiology
- Web of Science ID
- WOS:000441759600001
- Scopus ID
- 2-s2.0-85050803986
- Other Identifier
- 991019168965904721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Cell Biology