Disrupting assembly of the inner membrane complex blocks Plasmodium falciparum sexual stage development

Molly Parkyn Schneider; Boyin Liu; Philipp Glock; Annika Suttie; Emma McHugh; Dean Andrew; Steven Batinovic; Nicholas Williamson; Eric Hanssen; Paul McMillan; Marion Hliscs; Leann Tilley; Matthew W A Dixon

doi:10.1371/journal.ppat.1006659

Disrupting assembly of the inner membrane complex blocks Plasmodium falciparum sexual stage development

PLoS Pathog. 2017 Oct 6;13(10):e1006659. doi: 10.1371/journal.ppat.1006659. eCollection 2017 Oct.

Authors

Affiliations

¹ Department of Biochemistry and Molecular Biology, The University of Melbourne, Melbourne, Victoria, Australia.
² Mass Spectrometry and Proteomics Facility, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, Victoria, Australia.
³ Melbourne Advance Microscopy Facility, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, Victoria, Australia.
⁴ Biological Optical Microscopy Platform, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, Victoria, Australia.

Abstract

Transmission of malaria parasites relies on the formation of a specialized blood form called the gametocyte. Gametocytes of the human pathogen, Plasmodium falciparum, adopt a crescent shape. Their dramatic morphogenesis is driven by the assembly of a network of microtubules and an underpinning inner membrane complex (IMC). Using super-resolution optical and electron microscopies we define the ultrastructure of the IMC at different stages of gametocyte development. We characterize two new proteins of the gametocyte IMC, called PhIL1 and PIP1. Genetic disruption of PhIL1 or PIP1 ablates elongation and prevents formation of transmission-ready mature gametocytes. The maturation defect is accompanied by failure to form an enveloping IMC and a marked swelling of the digestive vacuole, suggesting PhIL1 and PIP1 are required for correct membrane trafficking. Using immunoprecipitation and mass spectrometry we reveal that PhIL1 interacts with known and new components of the gametocyte IMC.

MeSH terms

Animals
Microscopy, Electron / methods
Microtubules / metabolism*
Microtubules / ultrastructure
Plasmodium falciparum / growth & development*
Plasmodium falciparum / ultrastructure
Protein Transport
Sexual Development / physiology*

Grants and funding

MH was supported by the Deutsche Forschungsgemeinschaft (HL65/1-1) (http://www.dfg.de/en/index.jsp). LT is a Georgina Sweet, Australian Research Council Laureate Fellow (LE150100011) (http://www.arc.gov.au). MWAD and LT thank the Australian Research Council (DP110100624) (http://www.arc.gov.au) and the National Health and Medical Research Council (1098992) (https://www.nhmrc.gov.au) for funding this work. MWAD was supported by a National Health and Medical Research Council Training fellowship (602541). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.