Intraflagellar transport (IFT) is essential for cilium and flagellar assembly. This movement is accomplished by two IFT complexes: A and B. IFT88, intraflagellar protein 88, is a core element of IFT complex B. This protein has been linked to migration, to olfactory function, spindle formation and to mitosis. Recently, IFT88 was identified as a TCTEX1D4 interacting protein in human testis, suggesting a role in male reproduction. To broaden the knowledge on IFT88 function, particularly in testis and spermatozoa, an in silico analysis of IFT88 and IFT88 interactome was undertaken. IFT88 appears to be prone to protein-protein interactions, involved in spermatogenesis and since it interacts with key proteins related to male fertility, it may have a role in reproduction.
KeywordsIntraflagellar Protein 88 HomologSpermatozoaNetwork
Kozminski, K.G., Johnson, K.A., Forscher, P. and Rosenbaum, J.L. (1993) A Motility in the Eukaryotic Flagellum Unrelated to Flagellar Beating. Proceedings of the National Academy of Sciences of the United States of America, 90, 5519-5523. http://dx.doi.org/10.1073/pnas.90.12.5519
Hao, L. and Scholey, J.M. (2009) Intraflagellar Transport at a Glance. Journal of Cell Science, 122, 889-892. http://dx.doi.org/10.1242/jcs.023861
Scholey, J.M. and Anderson, K.V. (2006) Intraflagellar Transport and Cilium-Based Signaling. Cell, 125, 439-442. http://dx.doi.org/10.1016/j.cell.2006.04.013
Bhogaraju, S., Engel, B.D. and Lorentzen, E. (2013) Intraflagellar Transport Complex Structure and Cargo Interactions. Cilia, 2, 10. http://dx.doi.org/10.1186/2046-2530-2-10
Badano, J.L., Mitsuma, N., Beales, P.L. and Katsanis, N. (2006) The Ciliopathies: An Emerging Class of Human Genetic Disorders. Annual Review of Genomics and Human Genetics, 7, 125-148. http://dx.doi.org/10.1146/annurev.genom.7.080505.115610
Absalon, S., Blisnick, T., Kohl, L., Toutirais, G., Dore, G., Julkowska, D., et al. (2008) Intraflagellar Transport and Functional Analysis of Genes Required for Flagellum Formation in Trypanosomes. Molecular Biology of the Cell, 19, 929-944. http://dx.doi.org/10.1091/mbc.E07-08-0749
Taschner, M., Bhogaraju, S. and Lorentzen, E. (2012) Architecture and Function of IFT Complex Proteins in Ciliogenesis. Differentiation, 83, S12-S22. http://dx.doi.org/10.1016/j.diff.2011.11.001
Delaval, B., Bright, A., Lawson, N.D. and Doxsey, S. (2011) The Cilia Protein IFT88 Is Required for Spindle Orientation in Mitosis. Nature Cell Biology, 13, 461-468. http://dx.doi.org/10.1038/ncb2202
Pazour, G.J., Dickert, B.L., Vucica, Y., Seeley, E.S., Rosenbaum, J.L., Witman, G.B., et al. (2000) Chlamydomonas IFT88 and Its Mouse Homologue, Polycystic Kidney Disease Gene tg737, Are Required for Assembly of Cilia and Flagella. The Journal of Cell Biology, 151, 709-718. http://dx.doi.org/10.1083/jcb.151.3.709
Schrick, J.J., Onuchic, L.F., Reeders, S.T., Korenberg, J., Chen, X.N., Moyer, J.H., et al. (1995) Characterization of the Human Homologue of the Mouse Tg737 Candidate Polycystic Kidney Disease Gene. Human Molecular Genetics, 4, 559-567. http://dx.doi.org/10.1093/hmg/4.4.559
You, N., Liu, W., Tang, L., Zhong, X., Ji, R., Zhang, N., et al. (2012) Tg737 Signaling Is Required for Hypoxia-Enhanced Invasion and Migration of Hepatoma Cells. Journal of Experimental Clinical Cancer Research, 31, 75. http://dx.doi.org/10.1186/1756-9966-31-75
McIntyre, J.C., Davis, E.E., Joiner, A., Williams, C.L., Tsai, I.C., Jenkins, P.M., et al. (2012) Gene Therapy Rescues Cilia Defects and Restores Olfactory Function in a Mammalian Ciliopathy Model. Nature Medicine, 18, 1423-1428. http://dx.doi.org/10.1038/nm.2860
Robert, A., Margall-Ducos, G., Guidotti, J.E., Bregerie, O., Celati, C., Brechot, C., et al. (2007) The Intraflagellar Transport Component IFT88/Polaris Is a Centrosomal Protein Regulating G1-S Transition in Non-Ciliated Cells. Journal of Cell Science, 120, 628-637. http://dx.doi.org/10.1242/jcs.03366
Freitas, M.J., Korrodi-Gregorio, L., Morais-Santos, F., da Cruz, E.S.E. and Fardilha, M. (2014) TCTEX1D4 Interactome in Human Testis: Unraveling the Function of Dynein Light Chain in Spermatozoa. Omics, 18, 242-253. http://dx.doi.org/10.1089/omi.2013.0133
Meng, Q., Lux, A., Holloschi, A., Li, J., Hughes, J.M., Foerg, T., et al. (2006) Identification of Tctex2beta, a Novel Dynein Light Chain Family Member That Interacts with Different Transforming Growth Factor-Beta Receptors. Journal of Biological Chemistry, 281, 37069-37080. http://dx.doi.org/10.1074/jbc.M608614200
Dinkel, H., Michael, S., Weatheritt, R.J., Davey, N.E., Van Roey, K., Altenberg, B., et al. (2012) ELM—The Database of Eukaryotic Linear Motifs. Nucleic Acids Research, 40, D242-D251. http://dx.doi.org/10.1093/nar/gkr1064
de Castro, E., Sigrist, C.J., Gattiker, A., Bulliard, V., Langendijk-Genevaux, P.S., Gasteiger, E., et al. (2006) ScanProsite: Detection of PROSITE Signature Matches and Prorule-Associated Functional and Structural Residues in Proteins. Nucleic Acids Research, 34, W362-W365. http://dx.doi.org/10.1093/nar/gkl124
Letunic, I., Doerks, T. and Bork, P. (2012) SMART 7: Recent Updates to the Protein Domain Annotation Resource. Nucleic Acids Research, 40, D302-D305. http://dx.doi.org/10.1093/nar/gkr931
Karpenahalli, M.R., Lupas, A.N. and Soding, J. (2007) TPRpred: A Tool for Prediction of TPR-, PPR- and SEL1-Like Repeats from Protein Sequences. BMC Bioinformatics, 8, 2. http://dx.doi.org/10.1186/1471-2105-8-2
Blom, N., Sicheritz-Ponten, T., Gupta, R., Gammeltoft, S. and Brunak, S. (2004) Prediction of Post-Translational Glycosylation and Phosphorylation of Proteins from the Amino Acid Sequence. Proteomics, 4, 1633-1649. http://dx.doi.org/10.1002/pmic.200300771
Blom, N., Gammeltoft, S. and Brunak, S. (1999) Sequence and structure-Based Prediction of Eukaryotic Protein Phosphorylation Sites. Journal of Molecular Biology, 294, 1351-1362. http://dx.doi.org/10.1006/jmbi.1999.3310
de Castro, E., Sigrist, C.J., Gattiker, A., Bulliard, V., Langendijk-Genevaux, P.S., Gasteiger, E., et al. (2006) ScanProsite: Detection of PROSITE Signature Matches and ProRule-Associated Functional and Structural Residues in Proteins. Nucleic Acids Research, 34, W362-W365. http://dx.doi.org/10.1093/nar/gkl124
Petersen, T.N., Brunak, S., von Heijne, G. and Nielsen, H. (2011) SignalP 4.0: Discriminating Signal Peptides from Transmembrane Regions. Nature Methods, 8, 785-786. http://dx.doi.org/10.1038/nmeth.1701
Bologna, G., Yvon, C., Duvaud, S. and Veuthey, A.L. (2004) N-Terminal Myristoylation Predictions by Ensembles of Neural Networks. Proteomics, 4, 1626-1632. http://dx.doi.org/10.1002/pmic.200300783
Petersen, B., Petersen, T.N., Andersen, P., Nielsen, M. and Lundegaard, C. (2009) A Generic Method for Assignment of Reliability Scores Applied to Solvent Accessibility Predictions. BMC Structural Biology, 9, 51. http://dx.doi.org/10.1186/1472-6807-9-51
del-Toro, N., Dumousseau, M., Orchard, S., Jimenez, R.C., Galeota, E., Launay, G., et al. (2013) A New Reference Implementation of the PSICQUIC Web Service. Nucleic Acids Research, 41, W601-W606. http://dx.doi.org/10.1093/nar/gkt392
Hendrickx, A., Beullens, M., Ceulemans, H., Den Abt, T., Van Eynde, A., Nicolaescu, E., et al. (2009) Docking Motif- Guided Mapping of the Interactome of Protein Phosphatase-1. Chemistry Biology, 16, 365-371. http://dx.doi.org/10.1016/j.chembiol.2009.02.012
Reid, A.T., Redgrove, K., Aitken, R.J. and Nixon, B. (2011) Cellular Mechanisms Regulating Sperm-Zona Pellucida Interaction. Asian Journal of Andrology, 13, 88-96. http://dx.doi.org/10.1038/aja.2010.74
Mannowetz, N., Kartarius, S., Wennemuth, G. and Montenarh, M. (2010) Protein Kinase CK2 and New Binding Partners during Spermatogenesis. Cellular and Molecular Life Sciences, CMLS, 67, 3905-3913. http://dx.doi.org/10.1007/s00018-010-0412-9
Lamb, J.R., Tugendreich, S. and Hieter, P. (1995) Tetratrico Peptide Repeat Interactions, To TPR or Not to TPR? Trends in Biochemical Sciences, 20, 257-259. http://dx.doi.org/10.1016/S0968-0004(00)89037-4
Barlow, C., Liyanage, M., Moens, P.B., Tarsounas, M., Nagashima, K., Brown, K., Rottinghaus, S., Jackson, S.P., Tagle, D., Ried, T. and Wynshaw-Boris, A. (1998) Atm Deficiency Results in Severe Meiotic Disruption as Early as Leptonema of Prophase I. Development, 125, 4007-4017.
Cohen, P.T. (2002) Protein Phosphatase 1—Targeted in Many Directions. Journal of Cell Science, 115, 241-256.
Yamazaki, H., Nakata, T., Okada, Y. and Hirokawa, N. (1995) KIF3A/B: A Heterodimeric Kinesin Superfamily Protein that Works as a Microtubule Plus End-Directed Motor for Membrane Organelle Transport. Journal of Cell Biology, 130, 1387-1399. http://dx.doi.org/10.1083/jcb.130.6.1387
Chen, J., Yu, L., Li, D., Gao, Q., Wang, J., Huang, X., Bi, G., Wu, H. and Zhao, S.Y. (2003) Human CRYL1, a Novel Enzyme-Crystallin Overexpressed in Liver and Kidney and Downregulated in 58% of Liver Cancer Tissues from 60 Chinese Patients, and Four New Homologs from Other Mammalians. Gene, 302, 103-113. http://dx.doi.org/10.1016/S0378-1119(02)01095-8
Erlich, H.A., Valdes, A.M., Julier, C., Mirel, D. and Noble, J.A. (2009) Evidence for Association of the TCF7 Locus with Type I Diabetes. Genes and Immunity, 10, S54-S59. http://dx.doi.org/10.1038/gene.2009.92
Guyot, R., Vincent, S., Bertin, J., Samarut, J. and Ravel-Chapuis, P. (2010) The Transforming Acidic Coiled Coil (TACC1) Protein Modulates the Transcriptional Activity of the Nuclear Receptors TR and RAR. BMC Molecular Biology, 11, 3. http://dx.doi.org/10.1186/1471-2199-11-3
Hou, X., Mrug, M., Yoder, B.K., Lefkowitz, E.J., Kremmidiotis, G., D’Eustachio, P., Beier, D.R. and Guay-Woodford, L.M. (2002) Cystin, a Novel Cilia-Associated Protein, Is Disrupted in the cpk Mouse Model of Polycystic Kidney Disease. Journal of Clinical Investigation, 109, 533-540. http://dx.doi.org/10.1172/JCI0214099
Hu, S.S., Sun, W.Y., Wei, W., Wang, D., Jin, J., Wu, J.J., Chen, J.Y., Wu, H.X. and Wang, Q.T. (2013) Involvement of the Prostaglandin E Receptor EP2 in Paeoniflorin-Induced Human Hepatoma Cell Apoptosis. Anticancer Drugs, 24, 140-149. http://dx.doi.org/10.1097/CAD.0b013e32835a4dac
Murakami, H., Mizuno, T., Taniguchi, T., Fujii, M., Ishiguro, F., Fukui, T., et al. (2011) LATS2 Is a Tumor Suppressor Gene of Malignant Mesothelioma. Cancer Research, 71, 873-883. http://dx.doi.org/10.1158/0008-5472.CAN-10-2164
Pontoglio, M. (2000) Hepatocyte Nuclear Factor 1, a Transcription Factor at the Crossroads of Glucose Homeostasis. Journal of the American Society of Nephrology, 11, S140-S143.
To, S.Q., Takagi, K., Miki, Y., Suzuki, K., Abe, E., Yang, Y., Sasano, H., Simpson, E.R., Knower, K.C. and Clyne, C.D. (2012) Epigenetic Mechanisms Regulate the Prostaglandin E Receptor 2 in Breast Cancer. Journal of Steroid Biochemistry and Molecular Biology, 132, 331-338. http://dx.doi.org/10.1016/j.jsbmb.2012.07.007
Zheng, M., Zheng, K., Zhou, J.F., Sun, H.Y., Huang, L.F. and Liu, W.L. (2012) Tcf-1 Gene Silence Suppresses Downstream Gene Expression in CD4(+) T Cells from Bone Marrow of Aplastic Anemia Patients. Annals of Hematology, 91, 353-358. http://dx.doi.org/10.1007/s00277-011-1314-0