Analysis of Protein Palmitoylation Reveals a Pervasive Role in Plasmodium Development and Pathogenesis

Overview

Journal Cell Host Microbe

Publisher Cell Press

Specialties Infectious Diseases
Microbiology

Date 2012 Aug 21

PMID 22901544

Citations 102

Authors

Matthew L Jones

Mark O Collins

David Goulding

Jyoti S Choudhary

Julian C Rayner

Affiliations

Soon will be listed here.

Abstract

Asexual stage Plasmodium falciparum replicates and undergoes a tightly regulated developmental process in human erythrocytes. One mechanism involved in the regulation of this process is posttranslational modification (PTM) of parasite proteins. Palmitoylation is a PTM in which cysteine residues undergo a reversible lipid modification, which can regulate target proteins in diverse ways. Using complementary palmitoyl protein purification approaches and quantitative mass spectrometry, we examined protein palmitoylation in asexual-stage P. falciparum parasites and identified over 400 palmitoylated proteins, including those involved in cytoadherence, drug resistance, signaling, development, and invasion. Consistent with the prevalence of palmitoylated proteins, palmitoylation is essential for P. falciparum asexual development and influences erythrocyte invasion by directly regulating the stability of components of the actin-myosin invasion motor. Furthermore, P. falciparum uses palmitoylation in diverse ways, stably modifying some proteins while dynamically palmitoylating others. Palmitoylation therefore plays a central role in regulating P. falciparum blood stage development.

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References

Martin B, Cravatt B . Large-scale profiling of protein palmitoylation in mammalian cells. Nat Methods. 2009; 6(2):135-8. PMC: 2775068. DOI: 10.1038/nmeth.1293. View

Nkrumah L, Muhle R, Moura P, Ghosh P, Hatfull G, Jacobs Jr W . Efficient site-specific integration in Plasmodium falciparum chromosomes mediated by mycobacteriophage Bxb1 integrase. Nat Methods. 2006; 3(8):615-21. PMC: 2943413. DOI: 10.1038/nmeth904. View

Roth A, Wan J, Bailey A, Sun B, Kuchar J, Green W . Global analysis of protein palmitoylation in yeast. Cell. 2006; 125(5):1003-13. PMC: 2246083. DOI: 10.1016/j.cell.2006.03.042. View

Lasonder E, Ishihama Y, Andersen J, Vermunt A, Pain A, Sauerwein R . Analysis of the Plasmodium falciparum proteome by high-accuracy mass spectrometry. Nature. 2002; 419(6906):537-42. DOI: 10.1038/nature01111. View

Treeck M, Sanders J, Elias J, Boothroyd J . The phosphoproteomes of Plasmodium falciparum and Toxoplasma gondii reveal unusual adaptations within and beyond the parasites' boundaries. Cell Host Microbe. 2011; 10(4):410-9. PMC: 3254672. DOI: 10.1016/j.chom.2011.09.004. View

Resh M . Use of analogs and inhibitors to study the functional significance of protein palmitoylation. Methods. 2006; 40(2):191-7. PMC: 1712572. DOI: 10.1016/j.ymeth.2006.04.013. View

Murray C, Rosenfeld L, Lim S, Andrews K, Foreman K, Haring D . Global malaria mortality between 1980 and 2010: a systematic analysis. Lancet. 2012; 379(9814):413-31. DOI: 10.1016/S0140-6736(12)60034-8. View

Bozdech Z, Llinas M, Pulliam B, Wong E, Zhu J, DeRisi J . The transcriptome of the intraerythrocytic developmental cycle of Plasmodium falciparum. PLoS Biol. 2003; 1(1):E5. PMC: 176545. DOI: 10.1371/journal.pbio.0000005. View

Shipston M . Ion channel regulation by protein palmitoylation. J Biol Chem. 2011; 286(11):8709-16. PMC: 3058972. DOI: 10.1074/jbc.R110.210005. View

10.

Moon R, Taylor C, Bex C, Schepers R, Goulding D, Janse C . A cyclic GMP signalling module that regulates gliding motility in a malaria parasite. PLoS Pathog. 2009; 5(9):e1000599. PMC: 2742896. DOI: 10.1371/journal.ppat.1000599. View

11.

Mitchell D, Vasudevan A, Linder M, Deschenes R . Protein palmitoylation by a family of DHHC protein S-acyltransferases. J Lipid Res. 2006; 47(6):1118-27. DOI: 10.1194/jlr.R600007-JLR200. View

12.

Moskes C, Burghaus P, Wernli B, Sauder U, Durrenberger M, Kappes B . Export of Plasmodium falciparum calcium-dependent protein kinase 1 to the parasitophorous vacuole is dependent on three N-terminal membrane anchor motifs. Mol Microbiol. 2004; 54(3):676-91. DOI: 10.1111/j.1365-2958.2004.04313.x. View

13.

Yang W, Di Vizio D, Kirchner M, Steen H, Freeman M . Proteome scale characterization of human S-acylated proteins in lipid raft-enriched and non-raft membranes. Mol Cell Proteomics. 2009; 9(1):54-70. PMC: 2808267. DOI: 10.1074/mcp.M800448-MCP200. View

14.

Baum J, Richard D, Healer J, Rug M, Krnajski Z, Gilberger T . A conserved molecular motor drives cell invasion and gliding motility across malaria life cycle stages and other apicomplexan parasites. J Biol Chem. 2005; 281(8):5197-208. DOI: 10.1074/jbc.M509807200. View

15.

Rocks O, Peyker A, Kahms M, Verveer P, Koerner C, Lumbierres M . An acylation cycle regulates localization and activity of palmitoylated Ras isoforms. Science. 2005; 307(5716):1746-52. DOI: 10.1126/science.1105654. View

16.

Rees-Channer R, Martin S, Green J, Bowyer P, Grainger M, Molloy J . Dual acylation of the 45 kDa gliding-associated protein (GAP45) in Plasmodium falciparum merozoites. Mol Biochem Parasitol. 2006; 149(1):113-6. DOI: 10.1016/j.molbiopara.2006.04.008. View

17.

Levental I, Lingwood D, Grzybek M, Coskun U, Simons K . Palmitoylation regulates raft affinity for the majority of integral raft proteins. Proc Natl Acad Sci U S A. 2010; 107(51):22050-4. PMC: 3009825. DOI: 10.1073/pnas.1016184107. View

18.

Jones M, Kitson E, Rayner J . Plasmodium falciparum erythrocyte invasion: a conserved myosin associated complex. Mol Biochem Parasitol. 2006; 147(1):74-84. DOI: 10.1016/j.molbiopara.2006.01.009. View

19.

Xu G, Paige J, Jaffrey S . Global analysis of lysine ubiquitination by ubiquitin remnant immunoaffinity profiling. Nat Biotechnol. 2010; 28(8):868-73. PMC: 2946519. DOI: 10.1038/nbt.1654. View

20.

Wilson J, Raghavan A, Yang Y, Charron G, Hang H . Proteomic analysis of fatty-acylated proteins in mammalian cells with chemical reporters reveals S-acylation of histone H3 variants. Mol Cell Proteomics. 2010; 10(3):M110.001198. PMC: 3047146. DOI: 10.1074/mcp.M110.001198. View