Plasmodium Merozoite TRAP Family Protein Is Essential for Vacuole Membrane Disruption and Gamete Egress from Erythrocytes.
Surface-associated TRAP (thrombospondin-related anonymous protein) family proteins are conserved across the phylum of apicomplexan parasites. TRAP proteins are thought to play an integral role in parasite motility and cell invasion by linking the extracellular environment with the parasite submembrane actomyosin motor. Blood stage forms of the malaria parasite Plasmodium express a TRAP family protein called merozoite-TRAP (MTRAP) that has been implicated in erythrocyte invasion. Using MTRAP-deficient mutants of the rodent-infecting P. berghei and human-infecting P. falciparum parasites, we show that MTRAP is dispensable for erythrocyte invasion. Instead, MTRAP is essential for gamete egress from erythrocytes, where it is necessary for the disruption of the gamete-containing parasitophorous vacuole membrane, and thus for parasite transmission to mosquitoes. This indicates that motor-binding TRAP family members function not just in parasite motility and cell invasion but also in membrane disruption and cell egress.
Malaria Biology and Genetics Unit, Pasteur Institute, Paris 75015, France; Department of Parasitology, University of São Paulo-USP, São Paulo 05508-000, SP, Brazil. Electronic address: danielbargieri@gmail.com.
Daniel Y
DY
Bargieri
Malaria Biology and Genetics Unit, Pasteur Institute, Paris 75015, France.
Sabine
S
Thiberge
Department of Life Sciences, Imperial College London, South Kensington, London SW7 2AZ, UK.
Chwen L
CL
Tay
Malaria Biology and Genetics Unit, Pasteur Institute, Paris 75015, France; Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA.
Alison F
AF
Carey
Malaria Biology and Genetics Unit, Pasteur Institute, Paris 75015, France.
Alice
A
Rantz
Division of Cellular and Applied Infection Biology, Institute of Zoology, RWTH Aachen University, Aachen 52074, Germany.
Florian
F
Hischen
Inserm U1016, CNRS UMR 8104, Université Paris Descartes, Institut Cochin, Paris 75014, France.
Audrey
A
Lorthiois
Department of Life Sciences, Imperial College London, South Kensington, London SW7 2AZ, UK.
Ursula
U
Straschil
Malaria Parasite Biology and Vaccines Unit, Pasteur Institute, Paris 75015, France.
Pallavi
P
Singh
Malaria Parasite Biology and Vaccines Unit, Pasteur Institute, Paris 75015, France.
Shailja
S
Singh
The Walter and Eliza Hall Institute of Medical Research, Parkville 3052, VIC, Australia.
Tony
T
Triglia
Division of Malaria Research, Proteo-Science Center, Ehime University, Matsuyama, Ehime 790-8577, Japan.
Takafumi
T
Tsuboi
The Walter and Eliza Hall Institute of Medical Research, Parkville 3052, VIC, Australia; Department of Medical Biology, University of Melbourne, Parkville 3052, VIC, Australia.
Alan
A
Cowman
Malaria Parasite Biology and Vaccines Unit, Pasteur Institute, Paris 75015, France.
Chetan
C
Chitnis
Dipartimento di Malattie Infettive, Parassitarie ed Immunomediate, Istituto Superiore di Sanità, Rome 00161, Italy.
Pietro
P
Alano
Department of Life Sciences, Imperial College London, South Kensington, London SW7 2AZ, UK.
Jake
J
Baum
Division of Cellular and Applied Infection Biology, Institute of Zoology, RWTH Aachen University, Aachen 52074, Germany.
Gabriele
G
Pradel
Inserm U1016, CNRS UMR 8104, Université Paris Descartes, Institut Cochin, Paris 75014, France.
Catherine
C
Lavazec
Malaria Biology and Genetics Unit, Pasteur Institute, Paris 75015, France.
Robert
R
Ménard
D000818:Animals; D009033:Culicidae; D004912:Erythrocytes / Q000469:parasitology*; D005089:Exocytosis; D006801:Humans; D008566:Membranes / Q000378:metabolism; D052940:Merozoites / Q000502:physiology*; D051379:Mice; D010962:Plasmodium berghei / Q000502:physiology*; D010963:Plasmodium falciparum / Q000502:physiology*; D015800:Protozoan Proteins / Q000378:metabolism*; D014617:Vacuoles / Q000469:parasitology*
D015800:Protozoan Proteins