Premium
Identification of a Novel Trafficking Pathway Exporting Protein to the Nucleus via Classical Secretory Pathway in Plasmodium falciparum
Author(s) -
Sharma Rahul,
Sharma Bhumika,
Dhar Suman
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.565.5
Subject(s) - secretory pathway , microbiology and biotechnology , endoplasmic reticulum , golgi apparatus , rab , biology , protein subunit , nucleus , secretory protein , plasmodium falciparum , nuclear export signal , transport protein , secretion , cell nucleus , biochemistry , gtpase , gene , malaria , immunology
Malaria parasites use an extensive secretory pathway to export a number of proteins to remodel the host cells. It is involved in trafficking many proteins crucial for the parasite's survival. Despite the presence of a classical secretory pathway many of the intricacies involved in it still remain elusive. The Endoplasmic reticulum (ER) is the nerve center of the secretory pathway and it is involved in trafficking proteins to different organelles and outside of the parasite. In higher eukaryotes, ER membrane bound transcription factors such as SREBP are reported to get processed en route and migrate to the nucleus under the influence of specific cues. However, to the best of our knowledge, there is no report that a protein is constitutively trafficked to the nucleus by the classical secretory pathway. Herein, we report the presence of such a novel trafficking pathway in an apicomplexan, Plasmodium falciparum where a subunit of the Origin Recognition Complex (ORC), known for its role in DNA replication initiation, goes to the nucleus via ER‐Golgi secretory pathway. Based on several cell and molecular biology techniques that include biochemical assays, confocal microscopy and several inhibitor based assays we have shown that this ORC subunit is processed in the ER by a possible protease Signal Peptide Peptidase following which the C terminal fragment migrates to the nucleus through the nuclear pore complex. Our work proposes a new paradigm in cell biology, highlighting the role of ER in unconventional protein trafficking and reports for the first time a protein getting trafficked through such a pathway. This pathway adds a new dimension to the biology of trafficking and may have significant implications in strategizing new prophylactic measures against malaria This work was supported by DBT (Goverment of India)