A malaria scavenger receptor‐like protein essential for parasite development

Abstract

SummaryMalaria parasites suffer severe losses in the mosquito as they cross the midgut, haemolymph and salivary gland tissues, in part caused by immune responses of the insect. The parasite compensates for these losses by multiplying during the oocyst stage to form the infectious sporozoites. Upon human infection, malaria parasites are again attenuated by sustained immune attack. Here, we report a single copy gene that is highly conserved amongst Plasmodium species that encodes a secreted protein named PxSR . The predicted protein is composed of a unique combination of metazoan protein domains that have been previously associated with immune recognition/ activation and lipid/protein adhesion interactions at the cell surface, namely: (i) scavenger receptor cysteine rich (SRCR); (ii) pentraxin (PTX); (iii) polycystine-1, lipoxygenase, alpha toxin (LH2/PLAT); (iv) Limulus clotting factor C, Coch-5b2 and Lgl1 (LCCL). In our assessment the PxSR molecule is completely novel in biology and is only found in Apicomplexa parasites. We show that PxSR is expressed in sporozoites of both human and rodent malaria species. Disruption of the PbSR gene in the rodent malaria parasite P. berghei results in parasites that form normal numbers of oocysts, but fail to produce any sporozoites. We suggest that, in addition to a role in sporogonic development, PxSR may have a multiplicity of functions.

Proteome Analysis of Plasmodium falciparum Extracellular Secretory Antigens at Asexual Blood Stages Reveals a Cohort of Proteins with Possible Roles in Immune Modulation and Signaling

“…Predicted functions of the observed proteins are indicative of their secretory and/or surface-associated nature. Notably the detection of LCCL domain-containing protein CCP1, a member of a previously reported family of Apicomplexa-specific secreted extracellular molecules, lent important support to the definition of extracellular secretory fraction of parasite-infected RBCs (23,24). 35 S-labeled and unlabeled ESAs from intact P. falciparum-infected erythrocytes.…”

“…Another such example of multiple stage expression is the Apicomplexa-specific LCCL domain-containing family of proteins. The protein CCP1, a member of this LCCL family, has been reported to be a secreted extracellular protein (23,24). Hence its detection in the ES fraction provided significant support to the definition of the extracellular nature of the prepared sample.…”

Maternally supplied S-acyl-transferase is required for crystalloid organelle formation and transmission of the malaria parasite

“…Lack of crystalloid formation also has been reported for null mutants of the crystalloid-resident LCCL protein PbSR (LAP1), although the block in sporogony is not absolute (8), and, more recently, also for parasites lacking LAP3 (9). Gene deletion mutants of additional LCCL/LAP protein family members (10,32,33), plasmepsin VI (34) and rhomboid 3 (35), which may be bona fide crystalloid residents, present similar phenotypes with respect to oocyst differentiation. In P. berghei, hemozoin-containing vacuoles accumulate around the crystalloid's edges (4,28).…”

The origins of apicomplexan sequence innovation

“…S3) and two combinations could be considered pan-phylum. The PxSR protein (containing a scavenger receptor cysteine-rich domain [PF00530] and LCCL domain [PF03815]) has been implicated in oocyst differentiation into sporozoites in P. berghei (Claudianos et al 2002). The second combination (Myosin head [PF00063] and WD repeat [PF00400]) has been shown to be located in the myonemes, structural filaments that form rings along the length of Gregarines (Heintzelman and Mateer 2008).…”