Malaria parasite centrins can assemble by Ca2+-inducible condensation

PLoS Pathog. 2023 Dec 27;19(12):e1011899. doi: 10.1371/journal.ppat.1011899. eCollection 2023 Dec.

Abstract

Centrins are small calcium-binding proteins that have a variety of roles and are universally associated with eukaryotic centrosomes. Rapid proliferation of the malaria-causing parasite Plasmodium falciparum in the human blood depends on a particularly divergent and acentriolar centrosome, which incorporates several essential centrins. Their precise mode of action, however, remains unclear. In this study calcium-inducible liquid-liquid phase separation is revealed as an evolutionarily conserved principle of assembly for multiple centrins from P. falciparum and other species. Furthermore, the disordered N-terminus and calcium-binding motifs are defined as essential features for reversible biomolecular condensation, and we demonstrate that certain centrins can form co-condensates. In vivo analysis using live cell STED microscopy shows liquid-like dynamics of centrosomal centrin. Additionally, implementation of an inducible protein overexpression system reveals concentration-dependent formation of extra-centrosomal centrin assemblies with condensate-like properties. The timing of foci formation and dissolution suggests that centrin assembly is regulated. This study thereby provides a new model for centrin accumulation at eukaryotic centrosomes.

MeSH terms

  • Animals
  • Calcium* / metabolism
  • Calcium-Binding Proteins / metabolism
  • Centrosome / metabolism
  • Humans
  • Parasites* / metabolism

Substances

  • Calcium
  • Calcium-Binding Proteins

Grants and funding

This work was supported by the German Research Foundation (DFG) 349355339 to J.G, the Human Frontiers Science Program (HFSP) CDA00013/2018-C to J.G, the Chica and Heinz Schaller Foundation to J.G, the Studienstiftung des Deutschen Volkes to Y.V, The German Research Foundation (DFG) 240245660 - SFB 1129 to M.G. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.