title: Specific expression and export of the Plasmodium falciparum Gametocyte EXported Protein-5 marks the gametocyte ring stage.
abstract: BACKGROUND
  Plasmodium falciparum sexual development plays a fundamental role in the transmission and spread of malaria. The ability to generate gametocytes can be lost during culture in vitro, often associated with the loss of a subtelomeric region of chromosome 9. Gametocytogenesis starts with erythrocyte invasion by a sexually committed merozoite, but the first available specific marker of sexual differentiation appears only from 24 h post invasion.
  
  
  METHODS
  Specific antibodies and gene fusions were produced to study the timing of expression and the sub-cellular localization of the P. falciparum Gametocyte EXported Protein-5 (PfGEXP5), encoded in the subtelomeric region of chromosome 9. Expression patterns were examined in wild-type parasites and in parasite lines mutated in the Apetala2-G (AP2-G) transcription factor, governing a cascade of early sexual stage specific genes.
  
  
  RESULTS
  PfGEXP5 is highly expressed in early sexual stages and it is actively exported to the infected erythrocyte cytoplasm from as early as 14 h post-invasion in haemozoin-free, ring stage-like parasites. The pattern of PfGEXP5 expression and export is similar in wild-type parasites and in independent AP2-G defective parasite lines unable to produce gametocytes.
  
  
  CONCLUSIONS
  PfGEXP5 represents the earliest post-invasion sexual stage marker described to date. This provides a tool that can be used to identify sexually committed ring stage parasites in natural infections. This early gametocyte marker would enable the identification and mapping of malaria transmission reservoirs in human populations and the study of gametocyte sequestration dynamics in infected individuals. The fact that regulation of PfGEXP5 does not depend on the AP2-G master regulator of parasite sexual development suggests that, after sexual commitment, differentiation progresses through multiple checkpoints in the early phase of gametocytogenesis.
authors: Dipartimento di Malattie Infettive, Parassitarie e Immunomediate, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Rome, Italy. martatiburcio@gmail.com.|The Francis Crick Institute, Mill Hill Laboratory, The Ridgeway, Mill Hill, London, NW7 1AA, UK. martatiburcio@gmail.com.
authors: Marta
authors: M
authors: Tibúrcio
authors: Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, VIC, Australia. matthew.dixon@unimelb.edu.au.
authors: Matthew W A
authors: MW
authors: Dixon
authors: Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, VIC, Australia. o.looker@student.unimelb.edu.au.
authors: Oliver
authors: O
authors: Looker
authors: Dipartimento di Malattie Infettive, Parassitarie e Immunomediate, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Rome, Italy. sumerayounis@hotmail.com.|Department of Parasitology, Biomedical Primate Research Centre, PO Box 306, 2280 GH, Rijswijk, The Netherlands. sumerayounis@hotmail.com.
authors: Sumera Younis
authors: SY
authors: Younis
authors: Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, VIC, Australia. ltilley@unimelb.edu.au.
authors: Leann
authors: L
authors: Tilley
authors: Dipartimento di Malattie Infettive, Parassitarie e Immunomediate, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Rome, Italy. alano@iss.it.
authors: Pietro
authors: P
authors: Alano
mesh_terms: D003593:Cytoplasm / Q000378:metabolism / Q000469:parasitology; D004912:Erythrocytes / Q000469:parasitology; D005786:Gene Expression Regulation; D006790:Host-Parasite Interactions / Q000235:genetics; D006801:Humans; D008018:Life Cycle Stages / Q000235:genetics*; D010963:Plasmodium falciparum / Q000235:genetics / Q000502:physiology*; D015800:Protozoan Proteins / Q000235:genetics* / Q000378:metabolism*
chemical_list: D015800:Protozoan Proteins