“…Therefore, the proper expression and packaging of such components is important for sporozoite development. 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.…”
Section: Discussionmentioning
confidence: 80%
“…S4) known for members of the LAP/ CCp protein family typical for the ookinete/oocyst-specific crystalloid organelle (8,26,27). Believed to act as a reservoir for proteins required for sporozoite development within the oocyst, these organelles are generated in ookinetes but dissolve in early oocysts and are absent in late oocysts (6,9). Focal localization of DHHC10::GFP in one or two spots was observed in ∼75% of ookinetes (n = 60).…”
Section: Dhhc10mentioning
confidence: 99%
“…Crystalloids are formed by the microtubule (MT)-dependent transport and assembly of endoplasmic reticulum-derived vesicles (9). Concomitantly, LAP proteins such as LAP3 are shuttled to common assembly points and incorporated into mature crystalloids.…”
Section: Dhhc10mentioning
confidence: 99%
“…Sporozoite formation in the oocyst finally requires the presence of a stage-specific organelle, the crystalloid, a multivesicular structure assembled in the ookinete and putative reservoir of proteins and lipids used during sporogony. Although this enigmatic organelle was discovered more than 40 y ago, its formation and function remain largely unknown (4)(5)(6)(7)(8)(9). Six LCCL proteins have been shown to reside within (9) and maintain the stability (8,9) of these organelles essential for sporogony (10).…”
Transmission of the malaria parasite from the mammalian host to the mosquito vector requires the formation of adequately adapted parasite forms and stage-specific organelles. Here we show that formation of the crystalloid-a unique and short-lived organelle of the Plasmodium ookinete and oocyst stage required for sporogonyis dependent on the precisely timed expression of the S-acyltransferase DHHC10. DHHC10, translationally repressed in female Plasmodium berghei gametocytes, is activated translationally during ookinete formation, where the protein is essential for the formation of the crystalloid, the correct targeting of crystalloid-resident protein LAP2, and malaria parasite transmission.T he malaria parasite is capable of infecting both the vertebrate host and mosquito vector. After a mosquito blood meal, sexual precursor cells rapidly differentiate into mature gametes. In the mosquito midgut, the gametes mate to form a zygote that develops further into the motile ookinete. After crossing the midgut epithelium and establishing a sessile oocyst, the ookinete gives rise to thousands of sporozoites capable of infecting a subsequent mammalian host (1).Sharing key organelles like the nucleus, endoplasmic reticulum, Golgi, and mitochondria with other eukaryotes, this parasite has evolved specialized, stage-specific structures that are necessary for developmental progression during parasite transmission. These include, for example, osmiophilic bodies (secretory vesicles) that release protein factors capable of lysing the parasitophorous vacuole and erythrocyte membranes, thus producing free gametes (2) and a gliding motility motor anchored to the inner membrane complex (IMC), allowing the ookinete to migrate across the mosquito midgut epithelium and establish an oocyst (3). Sporozoite formation in the oocyst finally requires the presence of a stage-specific organelle, the crystalloid, a multivesicular structure assembled in the ookinete and putative reservoir of proteins and lipids used during sporogony. Although this enigmatic organelle was discovered more than 40 y ago, its formation and function remain largely unknown (4-9). Six LCCL proteins have been shown to reside within (9) and maintain the stability (8, 9) of these organelles essential for sporogony (10).The morphological changes taking place during zygote-toookinete development and the generation of thousands of sporozoites inside a single oocyst require extensive protein translation and membrane biogenesis to support the formation of organelles and plasma membrane (PM) surrounding each new parasite. Onethird of the proteins identified in the oocyst and oocyst-derived (midgut) sporozoites of the human parasite Plasmodium falciparum are putatively membrane-bound (11). The targeting of such proteins to organelles, and perhaps formation of certain organelles per se, requires appropriate sorting signals, along with transmembrane (TM) domains to keep these factors in place. Posttranslational modifications, such as lipidation, can increase the affinity of a modif...
“…Therefore, the proper expression and packaging of such components is important for sporozoite development. 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.…”
Section: Discussionmentioning
confidence: 80%
“…S4) known for members of the LAP/ CCp protein family typical for the ookinete/oocyst-specific crystalloid organelle (8,26,27). Believed to act as a reservoir for proteins required for sporozoite development within the oocyst, these organelles are generated in ookinetes but dissolve in early oocysts and are absent in late oocysts (6,9). Focal localization of DHHC10::GFP in one or two spots was observed in ∼75% of ookinetes (n = 60).…”
Section: Dhhc10mentioning
confidence: 99%
“…Crystalloids are formed by the microtubule (MT)-dependent transport and assembly of endoplasmic reticulum-derived vesicles (9). Concomitantly, LAP proteins such as LAP3 are shuttled to common assembly points and incorporated into mature crystalloids.…”
Section: Dhhc10mentioning
confidence: 99%
“…Sporozoite formation in the oocyst finally requires the presence of a stage-specific organelle, the crystalloid, a multivesicular structure assembled in the ookinete and putative reservoir of proteins and lipids used during sporogony. Although this enigmatic organelle was discovered more than 40 y ago, its formation and function remain largely unknown (4)(5)(6)(7)(8)(9). Six LCCL proteins have been shown to reside within (9) and maintain the stability (8,9) of these organelles essential for sporogony (10).…”
Transmission of the malaria parasite from the mammalian host to the mosquito vector requires the formation of adequately adapted parasite forms and stage-specific organelles. Here we show that formation of the crystalloid-a unique and short-lived organelle of the Plasmodium ookinete and oocyst stage required for sporogonyis dependent on the precisely timed expression of the S-acyltransferase DHHC10. DHHC10, translationally repressed in female Plasmodium berghei gametocytes, is activated translationally during ookinete formation, where the protein is essential for the formation of the crystalloid, the correct targeting of crystalloid-resident protein LAP2, and malaria parasite transmission.T he malaria parasite is capable of infecting both the vertebrate host and mosquito vector. After a mosquito blood meal, sexual precursor cells rapidly differentiate into mature gametes. In the mosquito midgut, the gametes mate to form a zygote that develops further into the motile ookinete. After crossing the midgut epithelium and establishing a sessile oocyst, the ookinete gives rise to thousands of sporozoites capable of infecting a subsequent mammalian host (1).Sharing key organelles like the nucleus, endoplasmic reticulum, Golgi, and mitochondria with other eukaryotes, this parasite has evolved specialized, stage-specific structures that are necessary for developmental progression during parasite transmission. These include, for example, osmiophilic bodies (secretory vesicles) that release protein factors capable of lysing the parasitophorous vacuole and erythrocyte membranes, thus producing free gametes (2) and a gliding motility motor anchored to the inner membrane complex (IMC), allowing the ookinete to migrate across the mosquito midgut epithelium and establish an oocyst (3). Sporozoite formation in the oocyst finally requires the presence of a stage-specific organelle, the crystalloid, a multivesicular structure assembled in the ookinete and putative reservoir of proteins and lipids used during sporogony. Although this enigmatic organelle was discovered more than 40 y ago, its formation and function remain largely unknown (4-9). Six LCCL proteins have been shown to reside within (9) and maintain the stability (8, 9) of these organelles essential for sporogony (10).The morphological changes taking place during zygote-toookinete development and the generation of thousands of sporozoites inside a single oocyst require extensive protein translation and membrane biogenesis to support the formation of organelles and plasma membrane (PM) surrounding each new parasite. Onethird of the proteins identified in the oocyst and oocyst-derived (midgut) sporozoites of the human parasite Plasmodium falciparum are putatively membrane-bound (11). The targeting of such proteins to organelles, and perhaps formation of certain organelles per se, requires appropriate sorting signals, along with transmembrane (TM) domains to keep these factors in place. Posttranslational modifications, such as lipidation, can increase the affinity of a modif...
“…1). Disruption of lap genes in P. berghei , either individually or in pairs, gives rise to very similar loss-of-function phenotypes characterized by a failure of the oocyst to produce infective sporozoites [5], [6], [7], [8], [9], [10].Fig. 1Schematic diagram of Plasmodium LAP1-LAP6 (PlasmoDB IDs shown on the right hand side).…”
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