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Molecular Dissection of Novel Trafficking and Processing of the T oxoplasma gondii Rhoptry Metalloprotease Toxolysin‐1
Author(s) -
Hajagos Bettina E.,
Turetzky Jay M.,
Peng Eric D.,
Cheng Stephen J.,
Ryan Christopher M.,
Souda Puneet,
Whitelegge Julian P.,
Lebrun Maryse,
Dubremetz JeanFrancois,
Bradley Peter J.
Publication year - 2012
Publication title -
traffic
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.677
H-Index - 130
eISSN - 1600-0854
pISSN - 1398-9219
DOI - 10.1111/j.1600-0854.2011.01308.x
Subject(s) - rhoptry , biology , metalloproteinase , microbiology and biotechnology , toxoplasma gondii , matrix metalloproteinase , immunology , genetics , antibody , apicomplexa , malaria , plasmodium falciparum
T oxoplasma gondii utilizes specialized secretory organelles called rhoptries to invade and hijack its host cell. Many rhoptry proteins are proteolytically processed at a highly conserved S Φ XE site to remove organellar targeting sequences that may also affect protein activity. We have studied the trafficking and biogenesis of a secreted rhoptry metalloprotease with homology to insulysin that we named toxolysin‐1 ( TLN 1). Through genetic ablation and molecular dissection of TLN 1, we have identified the smallest rhoptry targeting domain yet reported and expanded the consensus sequence of the rhoptry pro‐domain cleavage site. In addition to removal of its pro‐domain, TLN 1 undergoes a C ‐terminal cleavage event that occurs at a processing site not previously seen in T oxoplasma rhoptry proteins. While pro‐domain cleavage occurs in the nascent rhoptries, processing of the C ‐terminal region precedes commitment to rhoptry targeting, suggesting that it is mediated by a different maturase, and we have identified residues critical for proteolysis. We have additionally shown that both pieces of TLN 1 associate in a detergent‐resistant complex, formation of which is necessary for trafficking of the C ‐terminal portion to the rhoptries. Together, these studies reveal novel processing and trafficking events that are present in the protein constituents of this unusual secretory organelle.