Abstract
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.
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