The Role of Palmitoylation for Protein Recruitment to the Inner Membrane Complex of the Malaria Parasite

Wetzel, Johanna; Herrmann, Susann; Swapna, Lakshmipuram S.; Prusty, Dhaneswar; Peter, Arun T. John; Kono, Maya; Saini, Sidharth; Nellimarla, Srinivas; Wong, Tatianna Wai Ying; Wilcke, Louisa; Ramsay, Olivia; Cabrera, Ana; Biller, Laura; Heincke, Dorothee; Mossman, Karen; Spielmann, Tobias; Ungermann, Christian; Parkinson, John; Gilberger, Tim‐Wolf

doi:10.1074/jbc.m114.598094

Cited by 44 publications

(59 citation statements)

References 67 publications

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“…A number of S-acylated proteins are localized in the inner membrane complex (IMC). IMC is a membranous two layered structure located underneath the plasma membrane, which IMC plays central roles in host cell invasion and cytokinesis in P. falciparum (Cavalier-Smith, 1993; Wetzel et al, 2015). In another parasite Toxoplasma gondii , S-acylated proteins were also proved to be involved in many physiological processes including motility, invasion and division (Beck et al, 2010; Frénal et al, 2010, 2014).…”

Section: S-acylationmentioning

confidence: 99%

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Progress toward Understanding Protein S-acylation: Prospective in Plants

2017

Front. Plant Sci.

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S-acylation, also known as S-palmitoylation or palmitoylation, is a reversible post-translational lipid modification in which long chain fatty acid, usually the 16-carbon palmitate, covalently attaches to a cysteine residue(s) throughout the protein via a thioester bond. It is involved in an array of important biological processes during growth and development, reproduction and stress responses in plant. S-acylation is a ubiquitous mechanism in eukaryotes catalyzed by a family of enzymes called Protein S-Acyl Transferases (PATs). Since the discovery of the first PAT in yeast in 2002 research in S-acylation has accelerated in the mammalian system and followed by in plant. However, it is still a difficult field to study due to the large number of PATs and even larger number of putative S-acylated substrate proteins they modify in each genome. This is coupled with drawbacks in the techniques used to study S-acylation, leading to the slower progress in this field compared to protein phosphorylation, for example. In this review we will summarize the discoveries made so far based on knowledge learnt from the characterization of protein S-acyltransferases and the S-acylated proteins, the interaction mechanisms between PAT and its specific substrate protein(s) in yeast and mammals. Research in protein S-acylation and PATs in plants will also be covered although this area is currently less well studied in yeast and mammalian systems.

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Section: S-acylationmentioning

confidence: 99%

“…The only PAT/substrate pair characterized was in P. falciparum where PfDHHC1, an apicomplexan-specific and inner membrane complex-localized PAT, has identical expression pattern to two S-acylated proteins PfISP1 and PfISP3 (Wetzel et al, 2015). …”

Section: Protein S-acyl Transferases (Pats)mentioning

confidence: 99%

Progress toward Understanding Protein S-acylation: Prospective in Plants

2017

Front. Plant Sci.

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“…Despite the known localization data for several Plasmodium PATs (14,17,19), the specific functions of individual S-acyl-transferases for life cycle progression are almost completely unknown; only recently has DHHC2 been identified as being required for ookinete morphogenesis, specifically zygote elongation, and as…”

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confidence: 99%

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

Santos

Duarte

Kehrer

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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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...

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“…Pb IMC1c contains no other predicted sites for post-translational lipidation, indicating that its core alveolin domain is solely sufficient for IMC targeting. This contrasts with palmitoylation of the IMC sub-compartment proteins (ISPs), which was shown to be necessary for correct IMC targeting of ISPs in both Toxoplasma gondii and P. falciparum [27], [28]. In sharp contrast to IMC1c, mutation of equivalent cysteine motifs in the sporozoite-expressed alveolin IMC1a in P. berghei were recently shown to have a marked adverse effect on the protein's stability and, consequently, on parasite fitness [13].…”

Section: Discussionmentioning

confidence: 99%