Snapin, Positive Regulator of Stimulation- Induced Ca(2+) Release through RyR, Is Necessary for HIV-1 Replication in T Cells.

Authors

Shigemi M Kinoshita, Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University; Laboratory of Immune Regulation, Osaka University Graduate School of Frontier BiosciencesFollow
Amane Kogure, Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson UniversityFollow
Shizuka Taguchi, Laboratory of Immune Regulation, Osaka University Graduate School of Frontier Biosciences
Garry P Nolan, Department of Molecular Pharmacology, Stanford University School of Medicine; Department of Microbiology and Immunology, Stanford University School of MedicineFollow

Document Type

Article

Publication Date

10-10-2013

Comments

This article has been peer reviewed and is published in PloS One.

Volume 8, Issue 10, 10 October 2013, Article number e75297.

The published version is available at DOI: 10.1371/journal.pone.0075297.

© 2013 Kinoshita et al.

Abstract

To identify critical host factors necessary for human immunodeficiency virus 1 (HIV-1) replication, large libraries of short-peptide-aptamers were expressed retrovirally. The target of one inhibitor peptide, Pep80, identified in this screen was determined to be Snapin, a protein associated with the soluble N-ethyl maleimide sensitive factor adaptor protein receptor (SNARE) complex that is critical for calcium-dependent exocytosis during neurotransmission. Pep80 inhibited Ca(2+) release from intracellular stores and blocked downstream signaling by direct interruption of the association between Snapin and an intracellular calcium release channel, the ryanodine receptor (RyR). NFAT signaling was preferentially abolished by Pep80. Expression of Snapin overcame Pep80-mediated inhibition of Ca(2+)/NFAT signaling and HIV-1 replication. Furthermore, Snapin induced HIV-1 replication in primary CD4(+) T cells. Thus, through its interaction with RyR, Snapin is a critical regulator of Ca(2+) signaling and T cell activation. Use of the genetically selected intracellular aptamer inhibitors allowed us to define unique mechanisms important to HIV-1 replication and T cell biology.

Recommended Citation

Kinoshita, Shigemi M; Kogure, Amane; Taguchi, Shizuka; and Nolan, Garry P, "Snapin, Positive Regulator of Stimulation- Induced Ca(2+) Release through RyR, Is Necessary for HIV-1 Replication in T Cells." (2013). Department of Microbiology and Immunology Faculty Papers. Paper 49.
https://jdc.jefferson.edu/mifp/49

PubMed ID

24130701