Journal of Proteome Research ’ ACKNOWLEDGMENT We thank Derrick Mathias, Rebecca Pastrana-Mena, and Jennifer Armistead for critical review of the manuscript and Nathan J. Edwards for additional bioinformatics and com- puting support. This work was supported in part by grants K22AI077707-02 and R01AI082587-01 to R.R.D and fellowship support from 5T32AI007417-17 for L.A.P. from the NIAID, NIH; grant HHSN268201000032C (N01 HV-00240) from NHLBI to D.R.G., as well as seed funding from the Bloomberg Family Foundation to R.R.D. ’ ABBREVIATIONS AHC, agglomerative hierarchical clustering; BBMV, brush bor- der microvilli vesicles; DRM, detergent resistant membranes; DTT, dithiothreitol; FDR, false discovery rate; GPI, glycosylpho- sphotidyl inositol; LC, liquid chromatography; PI-PLC, phos- photidylinositol-speciﬁc phospholipase; PM, peritrophic matrix; PVM, parasitophorous vacuole membrane; TBV, transmission blocking vaccine; TFA, triﬂuoroacetic acid ’ REFERENCES (1) Dinglasan, R. R.; Jacobs-Lorena, M. Flipping the paradigm on malaria transmission-blocking vaccines. Trends Parasitol. 2008, 24 (28), 364–370. (2) Dinglasan, R. R.; Jacobs-Lorena, M. Insight into a conserved lifestyle: protein-carbohydrate adhesion strategies of vector-borne pathogens. Infect. Immun. 2005, 73 (12), 7797–7807. (3) Lavazec, C.; Bourgouin, C. Mosquito-based transmission-block- ing vaccines for interrupting Plasmodium development. Microbes Infect. 2008, 10 (8), 845–849. (4) Harris, T. J.; Siu, C. H. Reciprocal raft-receptor interactions and the assembly of adhesion complexes. BioEssays: News Rev. Mol., Cell. Dev. Biol. 2002, 24 (11), 996–1003. (5) Simons, K.; Gerl, M. J. Revitalizing membrane rafts: new tools and insights. Nat. Rev. Mol. Cell Biol. 2010, 11 (10), 688–99. (6) Simons, K.; Ikonen, E. Functional rafts in cell membranes. Nature 1997, 387 (6633), 569–572. (7) London, E.; Brown, D. A. Insolubility of lipids in triton X-100: Physical origin and relationship to sphingolipid/cholesterol membrane domains (rafts). Biochim. Biophys. Acta 2000, 1508 (1 2), 182–195. (8) Foster, L. J.; De Hoog, C. L.; Mann, M. Unbiased quantitative proteomics of lipid rafts reveals high speciﬁcity for signaling factors. Proc. Natl. Acad. Sci. U.S.A. 2003, 100 (10), 5813–5818. (9) Riethmuller, J.; Riehle, A.; Grassme, H.; Gulbins, E. Membrane rafts in host-pathogen interactions. Biochim. Biophys. Acta 2006, 1758 (12), 2139–2147. (10) Mittal, K.; Welter, B. H.; Temesvari, L. A. Entamoeba histoly- tica: lipid rafts are involved in adhesion of trophozoites to host extracellular matrix components. Exp. Parasitol. 2008, 120 (2), 127–134. (11) Dinglasan, R. R.; Kalume, D. E.; Kanzok, S. M.; Ghosh, A. K.; Muratova, O.; Pandey, A.; Jacobs-Lorena, M. Disruption of Plasmodium falciparum development by antibodies against a conserved mosquito midgut antigen. Proc. Natl. Acad. Sci. U.S.A. 2007, 104 (33), 13461– 13466. (12) Kotsyfakis, M.; Ehret-Sabatier, L.; Siden-Kiamos, I.; Mendoza, J.; Sinden, R. E.; Louis, C. Plasmodium berghei ookinetes bind to Anopheles gambiae and Drosophila melanogaster annexins. Mol. Micro- biol. 2005, 57 (1), 171–179. (13) Lavazec, C.; Bonnet, S.; Thiery, I.; Boisson, B.; Bourgouin, C. cpbAg1 encodes an active carboxypeptidase B expressed in the midgut of Anopheles gambiae. Insect Mol. Biol. 2005, 14 (2), 163–174. (14) Gonzalez-Lazaro, M.; Dinglasan, R. R.; Hernandez-Hernandez, F.; de, L.; Rodriguez, M. H.; Laclaustra, M.; Jacobs-Lorena, M.; Florez- Romo, L. Anopheles gambiae croquemort SCRBQ2, expression proﬁle ARTICLE in the mosquito and its potential interaction with the malaria parasite Plasmodium berghei. Insect Biochem. Mol. Biol. 2009, 39 (5 6), 395–402. (15) Rodríguez, M. C.; Martínez-Barnetche, J.; Alvarado-Delgado, A.; Batista, C.; Argotte-Ramos, R. S.; Hernandez-Martínez, S.; Gonzalez Ceron, L.; Torres, J. A.; Margos, G.; Rodríguez, M. H. The surface protein Pvs25 of Plasmodium vivax ookinetes interacts with calreticulin on the midgut apical surface of the malaria vector Anopheles albimanus. Mol. Biochem. Parasitol. 2007, 153 (2), 167–177. (16) King, J. Y.; Ferrara, R.; Tabibiazar, R.; Spin, J. M.; Chen, M. M.; Kuchinsky, A.; Vailaya, A.; Kincaid, R.; Tsalenko, A.; Deng, D. X.; Connolly, A.; Zhang, P.; Yang, E.; Watt, C.; Yakhini, Z.; Ben-Dor, A; Adler, A.; Bruhn, L.; Tsao, P.; Quertermous, T.; Ashley, E. A. Pathway analysis of coronary atherosclerosis. Physiol. Genomics 2005, 23 (1), 103–118. (17) Perkins, D. N.; Pappin, D. J.; Creasy, D. M.; Cottrell, J. S. Probability-based protein identiﬁcation by searching sequence databases using mass spectrometry data. Electrophoresis 1999, 20, 3551–3567. (18) Geer, L. Y.; Markey, S. P.; Kowalak, J. A.; Wagner, L.; Xu, M.; Maynard, D. M.; Yang, X.; Shi, W.; Bryant, S. H. Open mass spectro- metry search algorithm. J. Proteome Res. 2004, 3 (5), 958–964. (19) Craig, R.; Beavis, R. C. Tandem: matching proteins with tandem mass spectra. Bioinformatics 2004, 20 (9), 1466–1467. (20) Edwards, N.; Wu, X.; Tseng, C. W. An unsupervised, Model- Free, Machine-Learning Combiner for Peptide Identiﬁcations from Tandem Mass Spectra. Clin. Proteomics 2009, 5 (1), 23–36. (21) Hall, M.; Frank, E.; Holmes, G.; Pfahringer, B.; Reutemann, P.; Witten, I. H. The WEKA Data Mining Software: An Update. SIGKDD Explorations Newslett. 2009, 11, 1. (22) Ubaida Mohien, C.; Hartler, J.; Breitwieser, F.; Rix, U.; Rix, L. R.; Winter, G. E.; Thallinger, G. G.; Bennett, K. L.; Superti-Furga, G.; Trajanoski, Z.; Colinge, J. MASPECTRAS 2: An integration and analysis platform for proteomic data. Proteomics 2010, 10 (14), 2719–2722. (23) Jones, A. R.; Siepen, J. A.; Hubbard, S. J.; Paton, N. W. Improving sensitivity in proteome studies by analysis of false discovery rates for multiple search engines. Proteomics 2009, 9 (5), 1220–1229. (24) Dagda, R. K.; Sultana, T.; Lyons-Weiler, J. Evaluation of the Consensus of Four Peptide Identiﬁcation Algorithms for Tandem Mass Spectrometry Based Proteomics. J. Proteomics Bioinform. 2010, 3, 9–47. (25) Kapp, E. A.; Sch€utz, F.; Connolly, L. M.; Chakel, J. A.; Meza, J. E.; Miller, C. A.; Fenyo, D.; Eng, J. K.; Adkins, J. N.; Omenn, G. S.; Simpson, R. J. An evaluation, comparison, and accurate benchmarking of several publicly available MS/MS search algorithms: sensitivity and speciﬁcity analysis. Proteomics 2005, 5 (13), 3475–3490. (26) Oda, H.; Uemura, T.; Harada, Y.; Iwai, Y.; Takeichi, M. A Drosophila homolog of cadherin associated with armadillo and essential for embryonic cell-cell adhesion. Dev. Biol. 1994, 165 (2), 716–726. (27) Tepass, U.; Gruszynski-DeFeo, E.; Haag, T. A.; Omatyar, L.; Torok, T.; Hartenstein, V. Shotgun encodes Drosophila E-cadherin and is preferentially required during cell rearrangement in the neurectoderm and other morphogenetically active epithelia. Genes Dev. 1996, 10 (6), 672–685. (28) Devenport, M.; Fujioka, H.; Donnelly-Doman, M.; Shen, Z.; Jacobs-Lorena, M. Storage and secretion of Ag-Aper14, a novel peri- trophic matrix protein, and Ag-Muc1 from the mosquito Anopheles gambiae. Cell Tissue Res. 2005, 320 (1), 175–185. (29) Vlachou, D.; Schlegelmilch, T.; Christophides, G. K.; Kafatos, F. C. Functional genomic analysis of midgut epithelial responses in Anopheles during Plasmodium invasion. Curr. Biol. 2005, 15 (13), 1185–1195. (30) Dong, Y.; Aguilar, R.; Xi, Z.; Warr, E.; Mongin, E.; Dimopoulos, G. Anopheles gambiae immune responses to human and rodent Plasmodium parasite species. PLoS Pathog. 2006, 2 (6), e52. (31) Zdobnov, E. M.; von Mering, C.; Letunic, I.; Torrents, D.; Suyama, M.; Copley, R. R.; Christophides, G. K.; Thomasova, D.; Holt, R. A.; Subramanian, G. M.; Mueller, H. M.; Dimopoulos, G.; Law, J. H.; Wells, M. A.; Birney, E.; Charlab, R.; Halpern, A. L.; Kokoza, E.; Kraft, C. L.; Lai, Z.; Lewis, S.; Louis, C.; Barillas-Mury, C.; Nusskern, D.; Rubin, G. M.; Salzberg, S. L.; Sutton, G. G.; Topalis, P.; Wides, R.; 5161 dx.doi.org/10.1021/pr2006268 |J. Proteome Res. 2011, 10, 5150–5162