A conditional export system provides new insights into protein export in Plasmodium falciparum-infected erythrocytes

Theodora Saridaki1, Cecilia P Sanchez, Judith Pfahler

  • 1Hygiene Institut, Abteilung Parasitologie, Universitätsklinikum Heidelberg, Im Neuenheimer Feld 324, 69120 Heidelberg, Germany.

Cellular Microbiology
|August 12, 2008
PubMed

Insights

Researchers developed a new system to track how malaria parasites export virulence proteins. This method revealed that exported proteins interact with the molecular chaperone PfBiP during early export steps, clarifying the Plasmodium falciparum export pathway.

Area of Science:

  • Molecular parasitology
  • Cell biology
  • Infectious diseases

Background:

  • The malaria parasite Plasmodium falciparum exports virulence factors into the host erythrocyte.
  • The precise trafficking routes for these exported proteins remain poorly understood due to technical limitations.

Purpose of the Study:

  • To establish a conditional protein export system in P. falciparum to study the temporal dynamics of protein trafficking.
  • To identify intermediate steps and interacting factors during protein export.

Main Methods:

  • Development of a conditional protein export system using a conditional aggregation domain (CAD domain).
  • Fusion of the CAD domain to STEVOR and PfSBP1 to control export of soluble and transmembrane proteins.
  • Utilizing the system to study temporal events and identify interacting proteins.

Main Results:

  • The conditional export system successfully controlled the export of proteins to the erythrocyte cytosol and Maurer's clefts.
  • The system enabled the study of temporal sequences and identification of intermediate export steps.
  • Evidence was found for a physical interaction between exported proteins and the molecular chaperone PfBiP during early export.

Conclusions:

  • The developed conditional export system is a valuable tool for studying Plasmodium falciparum protein export.
  • The study identified PfBiP as an interacting factor during the early stages of protein export.
  • This work provides new insights into the molecular mechanisms of malaria parasite virulence factor trafficking.

Related Concept Videos

Malaria01:29

Malaria

Malaria pathogenesis in humans reflects a delicate interplay between parasite biology and host response. Clinical illness reflects a host’s immune response to the parasite’s asexual replication cycle, which is often asymptomatic in individuals with partial immunity. From the parasite's perspective, transmission between mosquito and human with minimal host pathology is evolutionarily advantageous. Among the six Plasmodium species infecting humans, P. falciparum and P. vivax dominate in global...
ABC Transporters: Exporter01:31

ABC Transporters: Exporter

ATP-binding cassette or ABC transporter is the largest superfamily of integral membrane proteins. The transporters have transmembrane-binding domains (TMDs) and nucleotide-binding domains (NBDs). The TMDs are specific to their substrates, whereas the NBDs are similar to engines that complete ATP hydrolysis to complete the substrate transport. They can be full transporters consisting of two TMDs and NBDs, half transporters with one TMD and NBD, while some encoded with a single TMD or NBD are...
Nuclear Export01:42

Nuclear Export

The nucleus restricts several proteins within and allows others to pass. The restricted proteins possess a nuclear retention sequence or NRS, anchoring them to the nuclear lamins and preventing their transport to the cytosol. The non-restricted proteins, after their synthesis, are transported to their site of action, such as the cytosol or other organelles, with the help of nuclear export signals or NES.
NES are of three types- the canonical 10-residue long leucine-rich signal and other...
Export of Misfolded Proteins out of the ER01:32

Export of Misfolded Proteins out of the ER

After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...