Trypanosome TOR complex 2 functions in cytokinesis

TOR (target of rapamycin) is a kinase of the phosphatidylinositol kinase-related kinase (PIKK) family that controls cell growth in eukaryotes in response to nutrients, energy conditions, and growth factors. We have recently identified two trypanosome TOR orthologs, named TbTOR1 and TbTOR2, and two other proteins with significant homology to yeast or mammalian TORs, named TbTOR-like 1 and TbTOR-like 2. TbTOR1 depletion results in arrest of bloodstream trypanosomes in G1, concomitant to protein synthesis inhibition; however, TbTOR2 depletion leads to dramatic morphological defects in cell polarization, endocytosis, and cytokinesis. Rapamycin inhibits T. brucei cell growth by prevention of TORC2 complex formation, without any effect on TORC1 contrary to what generally occurs in other eukaryotes. Based on the unique features of T. brucei and its distal position in the eukaryotic cell lineage, we describe our views on the function of the TOR protein as a major regulator of cell growth and cytokinesis and discuss a possible role in the developmental differentiation processes.

[1]  J. Crespo,et al.  Rapamycin inhibits trypanosome cell growth by preventing TOR complex 2 formation , 2008, Proceedings of the National Academy of Sciences.

[2]  P. Michels,et al.  Turnover of glycosomes during life-cycle differentiation of Trypanosoma brucei , 2008, Autophagy.

[3]  V. Turk,et al.  Autophagy Is Involved in Nutritional Stress Response and Differentiation in Trypanosoma cruzi* , 2008, Journal of Biological Chemistry.

[4]  J. Mottram,et al.  Cytokinesis in trypanosomatids. , 2007, Current opinion in microbiology.

[5]  K. Matthews,et al.  The cell biology of Trypanosoma brucei differentiation. , 2007, Current opinion in microbiology.

[6]  J. Crespo,et al.  Target of Rapamycin and LST8 Proteins Associate with Membranes from the Endoplasmic Reticulum in the Unicellular Green Alga Chlamydomonas reinhardtii , 2007, Eukaryotic Cell.

[7]  L. Tetley,et al.  Cysteine peptidases CPA and CPB are vital for autophagy and differentiation in Leishmania mexicana , 2006, Molecular microbiology.

[8]  D. Sabatini,et al.  Prolonged rapamycin treatment inhibits mTORC2 assembly and Akt/PKB. , 2006, Molecular cell.

[9]  D. Sabatini,et al.  Growing roles for the mTOR pathway. , 2005, Current opinion in cell biology.

[10]  M. Hall,et al.  The expanding TOR signaling network. , 2005, Current opinion in cell biology.

[11]  R. Loewith,et al.  Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitive , 2004, Nature Cell Biology.

[12]  D. Nolan,et al.  A differential role for actin during the life cycle of Trypanosoma brucei , 2004, The EMBO journal.

[13]  M. Hall,et al.  TOR2 is required for organization of the actin cytoskeleton in yeast. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[14]  K. Gull,et al.  *Author for correspondence , 2006 .