Targeting and sequestration of truncated Pfs230 in an intraerythrocytic compartment during Plasmodium falciparum gametocytogenesis.
For malaria to be transmitted, the Plasmodium falciparum parasite must invade an erythrocyte and undergo gametocytogenesis. When mature intraerythrocytic gametocytes are taken up in a blood meal by a mosquito they emerge as gametes and, once fertilized, continue to differentiate into infectious sporozoites. One of the major proteins associated with the surface of the parasite during gamete differentiation is Pfs230, a 360 kDa member of a family of P. falciparum proteins that contains a repeated cysteine motif domain. To characterize the role of different regions of Pfs230, the gene was disrupted by targeted integration and clones isolated that expressed distinct sections of Pfs230. Independent clones D1.356 a and b express the first 452 amino acids (aa) of Pfs230 and do not contain a cysteine motif domain, whereas clones D2.850 a and b express the first 950 aa, including the first cysteine motif domain. Although both sets of clones undergo gametogenesis and produce morphologically normal gametes, neither truncated Pfs230 is located on the surface of the gamete. In clones D1.356 a and b, the 452 aa Pfs230 is secreted into the parasitophorous vacuole and released as a soluble protein when the parasite emerges from the erythrocyte as a gamete. In marked contrast, the 950 aa form of Pfs230 expressed by clones D2.850 a and b is sequestered in a novel tubular compartment in the erythrocyte cytoplasm. This sexual-stage tubular intraerythrocytic compartment (STIC) is not recognized by antibodies specific for proteins associated with the parasitophorous vacuole membrane (Pfs16 or Exp-1) or Maurer's clefts (Pfsbp 1 or mAb LWL1) or intraerythrocytic asexual parasite proteins (PfEMP2 or HRP II).
Eksi
Saliha
S
Department of Biology, Loyola University Chicago, Chicago, IL 60626, USA.
Stump
Amy
A
Fanning
Sarah L
SL
Shenouda
Mary I
MI
Fujioka
Hisashi
H
Williamson
Kim C
KC
D000818:Animals; D000953:Antigens, Protozoan / Q000235:genetics / Q000502:physiology*; D000954:Antigens, Surface / Q000032:analysis / Q000235:genetics / Q000502:physiology; D015139:Blotting, Southern; D003546:Cysteine Endopeptidases / Q000494:pharmacology; D005718:Gametogenesis / Q000502:physiology*; D006056:Golgi Apparatus / Q000502:physiology; D018613:Microscopy, Confocal; D010963:Plasmodium falciparum / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D015800:Protozoan Proteins / Q000235:genetics / Q000502:physiology*; D011994:Recombinant Proteins; D014170:Transformation, Genetic
D000953:Antigens, Protozoan; D000954:Antigens, Surface; C430263:Pfs230 antigen, Plasmodium falciparum; D015800:Protozoan Proteins; D011994:Recombinant Proteins; D003546:Cysteine Endopeptidases