Identification of a novel trafficking pathway exporting a replication protein, Orc2 to nucleus via classical secretory pathway in Plasmodium falciparum

Biochim Biophys Acta Mol Cell Res. 2018 May;1865(5):817-829. doi: 10.1016/j.bbamcr.2018.03.003. Epub 2018 Mar 7.

Abstract

Malaria parasites use an extensive secretory pathway to traffic a number of proteins within itself and beyond. In higher eukaryotes, Endoplasmic Reticulum (ER) membrane bound transcription factors such as SREBP are reported to get processed en route and migrate to nucleus under the influence of specific cues. However, a protein constitutively trafficked to the nucleus via classical secretory pathway has not been reported. Herein, we report the presence of a novel trafficking pathway in an apicomplexan, Plasmodium falciparum where a homologue of an Origin Recognition Complex 2 (Orc2) goes to the nucleus following its association with the ER. Our work highlights the unconventional role of ER in protein trafficking and reports for the first time an ORC homologue getting trafficked through such a pathway to the nucleus where it may be involved in DNA replication and other ancillary functions. Such trafficking pathways may have a profound impact on the cell biology of a malaria parasite and have significant implications in strategizing new antimalarials.

Keywords: Classical secretory pathway; ER-nucleus traffic; Nuclear import; Origin recognition complex 2; Plasmodium falciparum; Protein trafficking.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Nucleus / genetics
  • DNA Replication / genetics
  • Endoplasmic Reticulum / genetics
  • Humans
  • Malaria, Falciparum / genetics*
  • Malaria, Falciparum / parasitology
  • Origin Recognition Complex / genetics*
  • Plasmodium falciparum / genetics*
  • Plasmodium falciparum / pathogenicity
  • Protein Transport / genetics*
  • Signal Transduction / genetics

Substances

  • Origin Recognition Complex