Comparative proteomics of vesicles essential for the egress of
Plasmodium falciparum gametocytes from red blood cells
Abstract
Transmission of malaria parasites to the mosquito is mediated by sexual
precursor cells, the gametocytes. Upon entering the mosquito midgut, the
gametocytes egress from the enveloping erythrocyte while passing through
gametogenesis. Egress follows an inside-out mode during which the
membrane of the parasitophorous vacuole ruptures prior to the
erythrocyte membrane. Membrane rupture requires the exocytosis of
specialized secretory vesicles of the parasites; i.e. the osmiophilic
bodies (OBs) involved in rupturing the parasitophorous vacuole membrane,
and vesicles (here termed g-exonemes) that harbour the perforin-like
protein PPLP2 required for erythrocyte lysis. While several OB proteins
are known, like G377 and MDV1/Peg3, the protein composition of the
g-exonemes remains unclear. Here, we used high-resolution imaging and
BioID methods to study the two types of egress vesicles in
Plasmodium falciparum gametocytes. We show that OB exocytosis
precedes discharge of the g-exonemes and that exocytosis of the
g-exonemes, but not of the OBs, is calcium-sensitive. Further, the two
types of vesicles exhibit distinct proteomes. In addition to known
egress-related proteins, our analyses revealed novel components of OBs
and g-exonemes, including proteins involved in vesicle trafficking. Our
data provide insight into the immense molecular machinery required for
the inside-out egress of P. falciparum gametocytes.