Research ArticleParasitology

The kinetoplastid-specific phosphatase KPP1 attenuates PLK activity to facilitate flagellum inheritance in Trypanosoma brucei

See allHide authors and affiliations

Science Signaling  09 Feb 2021:
Vol. 14, Issue 669, eabc6435
DOI: 10.1126/scisignal.abc6435

You are currently viewing the abstract.

View Full Text

Log in to view the full text

Log in through your institution

Log in through your institution

Passing the flagellum in trypanosomes

The single flagellum of the unicellular parasite Trypanosoma brucei is critical for virulence, and Polo-like kinase (TbPLK) is required for flagellum inheritance during T. brucei proliferation. An et al. found that flagellum inheritance required dephosphorylation of TbPLK Thr125 by the phosphatase KPP1 at flagellum-associated structures during specific phases of the cell cycle to reduce TbPLK activity. In the absence of this inhibition, flagellum inheritance was disrupted because of hyperphosphorylation of the TbPLK substrate TbCentrin2. In human and fish PLK homologs, dephosphorylation of serine residues corresponding to TbPLK Thr125 also reduces kinase activity, demonstrating conservation of this important mechanism for precisely regulating PLK activity during the cell cycle.


Trypanosoma brucei, an important human parasite, has a flagellum that controls cell motility, morphogenesis, proliferation, and cell-cell communication. Inheritance of the newly assembled flagellum during the cell cycle requires the Polo-like kinase homolog TbPLK and the kinetoplastid-specific protein phosphatase KPP1, although whether TbPLK acts on KPP1 or vice versa has been unclear. Here, we showed that dephosphorylation of TbPLK on Thr125 by KPP1 maintained low TbPLK activity in the flagellum-associated hook complex structure, thereby ensuring proper flagellum positioning and attachment. This dephosphorylation event required the recognition of phosphorylated Thr198 in the activation loop of TbPLK by the N-terminal Plus3 domain of KPP1 and the dephosphorylation of phosphorylated Thr125 in TbPLK by the C-terminal catalytic domain of KPP1. Dephosphorylation of TbPLK by KPP1 prevented hyperphosphorylation of the hook complex protein TbCentrin2, thereby allowing timely dephosphorylation of phosphorylated TbCentrin2 for hook complex duplication and flagellum positioning and attachment. Thus, KPP1 attenuates TbPLK activity by dephosphorylating TbPLK to facilitate flagellum inheritance.

View Full Text

Stay Connected to Science Signaling