Loss of protein remodels shape-shifting parasite

Parasites frequently undergo dramatic shape changes during their life cycles, but these transformations might not be as difficult as they appear, Hayes et al. suggest.

Trypanosoma brucei parasites cause African sleeping sickness. In their trypomastigote stage, the kinetoplast, which houses the cell’s mitochondrial DNA, is posterior to the nucleus, and almost all of the flagellum is connected to the cell. In the epimastigote stage, on the other hand, the kinetoplast is anterior to the nucleus, and only part of the flagellum is fastened to the cell. T. brucei’s close relatives come in many different shapes, indicating that the parasites have also altered their morphology during evolution.

When Hayes et al. used RNAi to quash a protein called ClpGM6 in T. brucei trypomastigotes, the cells switched to an epimastigote-like morphology. The kinetoplast was close to the nucleus or anterior to it, and a long section of the flagellum extended beyond the cell. The parasites weren’t identical to epimastigotes—they lacked a distinctive surface protein found at this life stage—but they were able to survive and reproduce for more than 40 generations.

ClpGM6 resides in the flagellar attachment zone (FAZ) and likely helps fasten the flagellum to the cell body. Loss of ClpGM6 shortened the FAZ, which defines the position of the cytokinetic furrow during division and hence determines cell size and shape. The study suggests that the dramatic morphological changes during the life cycle and during parasite evolution may result from adjustments in the levels of a few key proteins, rather than from wholesale changes in protein expression or in the genome.