e FKBP12 proteins are able to inhibit TOR kinases or calcineurin phosphatases upon binding of rapamycin or FK506 drugs, respectively. The Trypanosoma brucei FKBP12 homologue (TbFKBP12) was found to be a cytoskeleton-associated protein with specific localization in the flagellar pocket area of the bloodstream form. In the insect procyclic form, RNA interference-mediated knockdown of TbFKBP12 affected motility. In bloodstream cells, depletion of TbFKBP12 affected cytokinesis and cytoskeleton architecture. These last effects were associated with the presence of internal translucent cavities limited by an inside-out configuration of the normal cell surface, with a luminal variant surface glycoprotein coat lined up by microtubules. These cavities, which recreated the streamlined shape of the normal trypanosome cytoskeleton, might represent unsuccessful attempts for cell abscission. We propose that TbFKBP12 differentially affects stage-specific processes through association with the cytoskeleton.A frican trypanosomes are extracellular protozoan flagellated parasites responsible for sleeping sickness in humans and nagana in cattle. The life cycle of Trypanosoma brucei encompasses different stages, including the long slender bloodstream forms (BF) proliferating in mammalian blood and the procyclic forms (PF) that actively multiply in the gut of the Glossina vector (1).Trypanosomes are among the most divergent eukaryotes in evolution and display specific features, many of which are related to cell division probably due to the fact that most organelles are present at one copy per cell and have to be duplicated and segregated synchronously between the daughter cells. This division involves check points that differ from those of other eukaryotes, such as the control of karyokinesis when cytokinesis is inhibited (2, 3) and vice versa (4). Molecular effectors of these check points, such as mitogen-activated protein kinase and cyclin-dependent kinase, are present in trypanosomes but diverge in function compared to other eukaryotes (5, 6).The flagellum and its motility appear to play a key role in the control of cell division (7-9). This organelle initiates at the basal body, which is associated to the kinetoplast (10, 11), emerges from the flagellar pocket (FP), and it is attached along the cell body for most of its length by the flagellum attachment zone (FAZ). The flagellum contains a canonical axoneme and the paraflagellar rod (PFR) that are physically linked (12-14). The duplication and segregation of these structures are interdependent. During cytokinesis, the ingression of the cleavage furrow follows an axis in between the new and the old flagellum. The position and initiation of the furrow are closely related to the FAZ, as demonstrated by the study of flagellum mutants (15)(16)(17)(18)(19)(20)(21).In eukaryotes such as yeasts or mammals the TOR pathway is a major player in the control of cell division mediated by the action of two protein complexes, . These complexes contain the two different threonine/serine kinases T...