Interference of HTLV-1 Tax Protein with Cell Polarity Regulators: Defining the Subcellular Localization of the Tax-DLG1 Interaction

Viruses. 2017 Nov 23;9(12):355. doi: 10.3390/v9120355.

Abstract

Human T cell leukemia virus (HTLV)-1 Tax (Tax) protein is very important in viral replication and cell transformation. Tax localizes in the nucleus and cytoplasm in association with organelles. Some activities of Tax depend on interactions with PDZ (PSD-95/Discs Large/Z0-1) domain-containing proteins such as Discs large protein 1 (DLG1) which is involved in cell polarity and proliferation. The DLG1 interaction results in a cytoplasmic co-localization pattern resembling vesicular aggregates, the nature of which is still unknown. To further explore the role of PDZ proteins in HTLV-1 cell transformation, we deeply investigated the Tax-DLG1 association. By fluorescence resonance energy transfer (FRET), we detected, for the first time, the direct binding of Tax to DLG1 within the cell. We showed that the interaction specifically affects the cellular distribution of not only DLG1, but also Tax. After studying different cell structures, we demonstrated that the aggregates distribute into the Golgi apparatus in spatial association with the microtubule-organizing center (MTOC). This study contributes to understand the biological significance of Tax-PDZ interactions.

Keywords: DLG1; HTLV-1; PDZ; Tax; protein interactions.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Cell Nucleus / metabolism
  • Cell Polarity*
  • Cell Transformation, Viral
  • Cytoplasm / metabolism
  • Discs Large Homolog 1 Protein
  • Fluorescence Resonance Energy Transfer
  • Gene Expression Regulation
  • Gene Products, tax / genetics
  • Gene Products, tax / metabolism*
  • Golgi Apparatus / metabolism
  • HEK293 Cells
  • Human T-lymphotropic virus 1 / genetics
  • Human T-lymphotropic virus 1 / physiology*
  • Humans
  • Jurkat Cells
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Microscopy
  • Microtubule-Organizing Center / metabolism*
  • Protein Aggregates
  • Protein Transport
  • Virus Replication

Substances

  • Adaptor Proteins, Signal Transducing
  • DLG1 protein, human
  • Discs Large Homolog 1 Protein
  • Gene Products, tax
  • Membrane Proteins
  • Protein Aggregates
  • tax protein, Human T-lymphotrophic virus 1