Abstract
Regulated protein secretion is required for malaria parasite life cycle progression and transmission between the mammalian host and mosquito vector. During transmission from the host to the vector, exocytosis of highly specialised secretory vesicles, such as osmiophilic bodies, is key to the dissolution of the red blood cell and parasitophorous vacuole membranes enabling gamete egress. The positioning of adhesins from the TRAP family, from micronemes to the sporozoite surface, is essential for gliding motility of the parasite and transmission from mosquito to mammalian host. Here we identify a conserved role for the putative pantothenate transporter PAT in Plasmodium berghei in vesicle fusion of two distinct classes of vesicles in gametocytes and sporozoites. PAT is a membrane component of osmiophilic bodies in gametocytes and micronemes in sporozoites. Despite normal formation and trafficking of osmiophilic bodies to the cell surface upon activation, PAT-deficient gametes fail to discharge their contents, remain intraerythrocytic and unavailable for fertilisation and further development in the mosquito. Sporozoites lacking PAT fail to secrete TRAP, are immotile and thus unable to infect the subsequent rodent host. Thus, P. berghei PAT appears to regulate exocytosis in two distinct populations of vesicles in two different life cycle forms rather than acting as pantothenic transporter during parasite transmission.
Highlights
Malaria is a vector-borne disease caused by parasitic protozoans from the genus Plasmodium
PVM dissolution requires the exocytosis of so-called osmiophilic bodies (OB), electron dense organelles derived from Golgi vesicles [8] that are known to contain three types of unrelated proteins: G377, GEST and MDV1/ PEG3 [9,10,11,12,13,14]
In global proteomic screens PAT has been identified in P. berghei sporozoites [33], and the P. falciparum ortholog PF3D7_0206200 was detected in stage V gametocytes [34] as well as salivary gland sporozoites [35] but not asexual stage parasites
Summary
Malaria is a vector-borne disease caused by parasitic protozoans from the genus Plasmodium. During the blood meal the infected mosquito injects highly motile salivary gland sporozoites into a naïve host, or is itself infected if feeding on an individual harbouring gametocytes, sexual precursor cells that are intraerythrocytic [red blood cell (RBC) resident], immotile forms within the mammalian host. Gamete egress is triggered by the change in environmental conditions from those encountered in the circulatory system of the mammalian host [4, 6, 7] and is accomplished within 15 minutes It depends on the secretion of intracellular, vesicle-resident protein factors that facilitate lysis of the PVM and the RBCM [3, 4]. Perhaps additional but unknown factors, are released in concert to enable rapid breakdown of the PVM and RBCM
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
