A CLK1-KKT2 Signaling Pathway Regulating Kinetochore Assembly in Trypanosoma brucei
Manuel Saldivia, Adam J. M. Wollman, Juliana B. T. Carnielli, Nathaniel G. Jones, Mark C. Leake, Christopher Bower-Lepts, Srinivasa P. S. Rao, Jeremy C. Mottram
Abstract
In eukaryotic cells, kinetochores are large protein complexes that link chromosomes to dynamic microtubule tips, ensuring proper segregation and genomic stability during cell division. Several proteins tightly coordinate kinetochore functions, including the protein kinase aurora kinase B. The kinetochore has diverse evolutionary roots. For example, trypanosomatids, single-cell parasitic protozoa that cause several neglected tropical diseases, possess a unique repertoire of kinetochore components whose regulation during the cell cycle remains unclear. Here, we shed light on trypanosomatid kinetochore biology by showing that the protein kinase CLK1 coordinates the assembly of the inner kinetochore by phosphorylating one of its components, KKT2, allowing the timely spatial recruitment of the rest of the kinetochore proteins and posterior attachment to microtubules in a process that is aurora kinase B independent.