Histone acetylase GCN5 enters the nucleus via importin-α in protozoan parasite Toxoplasma gondii

Micah M. Bhatti, William J. Sullivan

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

The histone acetyltransferase GCN5 acetylates nucleosomal histones to alter gene expression. How GCN5 gains entry into the nucleus of the cell has not been determined. We have mapped a six-amino acid motif (RKRVKR) that serves as a necessary and sufficient nuclear localization signal (NLS) for GCN5 in the protozoan pathogen. Toxoplasma gondii (TgGCN5). Virtually nothing is known about nucleocytoplasmic transport in these parasites (phylum Apicomplexa), and this study marks the first demonstrated NLS delineated for members of the phylum. The TgGCN5 NLS has predictive value because it successfully identifies other nuclear proteins in three different apicomplexan genomic databases. Given the basic composition of the T. gondii NLS, we hypothesized that TgGCN5 physically interacts with importin-α, the main transport receptor in the importin/karyopherin nuclear import pathway. We cloned the importin-α gene from T. gondii (TgIMPα), which encodes a protein of 545 amino acids that possesses an importin-β-binding domain and armadillo/β-catenin-like repeats. In vitro co-immunoprecipitation experiments confirm that TgIMPα directly interacts with TgGCN5, but this interaction is abolished if the Tg-GCN5 NLS is deleted. Taken together, these data argue that TgGCN5 gains access to the parasite nucleus by interacting with TgIMPα. Bioinformatics analysis of the T. gondii genome reveals that other components of the importin pathway are present in the organism. This study demonstrates the utility of T. gondii as a model for the study of nucleocytoplasmic trafficking in early eukaryotic cells.

Original languageEnglish (US)
Pages (from-to)5902-5908
Number of pages7
JournalJournal of Biological Chemistry
Volume280
Issue number7
DOIs
StatePublished - Feb 18 2005

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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