A split-luciferase complementation, real-time reporting assay enables monitoring of the disease-associated transmembrane protein TREM2 in live cells

Journal of Biological Chemistry

Volumn 292, Issue 25, 2017, Pages 10651-10663

  Varnum, Megan M ^a   Clayton, Kevin A ^a   Yoshii Kitahara, Asuka ^a   Yonemoto, Grant ^a   Koro, Lacin ^a   Ikezu, Seiko ^a   Ikezu, Tsuneya ^a  

^a BOSTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMINO ACIDS; ANTIBODIES; ANTIGEN-ANTIBODY REACTIONS; BACTERIA; CELL CULTURE; CELLS; ENZYME ACTIVITY; NEURODEGENERATIVE DISEASES;

FLOW CYTOMETRY ANALYSIS; HUMAN EMBRYONIC KIDNEY 293 CELLS; NEURODEGENERATIVE DISORDERS; PROTEIN TYROSINE KINASE; PROTEIN-PROTEIN INTERACTIONS; SPLEEN TYROSINE KINASE; TRANS-MEMBRANE PROTEINS; TRANSIENT TRANSFECTION;

MOLECULAR BIOLOGY;

ADAPTOR PROTEIN; LUCIFERASE; PROTEIN ANTIBODY; PROTEIN KINASE SYK; PROTEIN TYROBP; TRIGGERING RECEPTOR EXPRESSED ON MYELOID CELLS 2; UNCLASSIFIED DRUG; IMMUNOGLOBULIN RECEPTOR; MEMBRANE PROTEIN; RENILLA LUCIFERIN 2 MONOOXYGENASE; SIGNAL TRANSDUCING ADAPTOR PROTEIN; SYK PROTEIN, HUMAN; SYK PROTEIN, MOUSE; TREM2 PROTEIN, HUMAN; TREM2 PROTEIN, MOUSE; TYROBP PROTEIN, HUMAN; TYROBP PROTEIN, MOUSE;

AMINO TERMINAL SEQUENCE; ANIMAL CELL; ARTICLE; BIOLUMINESCENCE; CARBOXY TERMINAL SEQUENCE; CONTROLLED STUDY; DIMERIZATION; ENZYME ACTIVITY; ENZYME LINKED IMMUNOSORBENT ASSAY; FLOW CYTOMETRY; GENETIC TRANSFECTION; HEK293 CELL LINE; HUMAN; HUMAN CELL; IN VITRO STUDY; MICROGLIA; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN INTERACTION ASSAY; PROTEIN PROTEIN INTERACTION; RENILLA; SIGNAL TRANSDUCTION; SPLIT LUCIFERASE COMPLEMENTATION ASSAY; STAPHYLOCOCCUS AUREUS; ALZHEIMER DISEASE; ANIMAL; CELL LINE; CHONDRODYSPLASIA; GENETIC COMPLEMENTATION; GENETICS; LIPODYSTROPHY; METABOLISM; PROCEDURES; SUBACUTE SCLEROSING PANENCEPHALITIS;

ADAPTOR PROTEINS, SIGNAL TRANSDUCING; ALZHEIMER DISEASE; ANIMALS; CELL LINE; FLOW CYTOMETRY; GENETIC COMPLEMENTATION TEST; HUMANS; LIPODYSTROPHY; LUCIFERASES, RENILLA; MEMBRANE GLYCOPROTEINS; MEMBRANE PROTEINS; MICE; MICROGLIA; OSTEOCHONDRODYSPLASIAS; RECEPTORS, IMMUNOLOGIC; SUBACUTE SCLEROSING PANENCEPHALITIS; SYK KINASE;

EID: 85021352419     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M116.759159     Document Type: Article

References (52)

1. Colonna, M. (2003) TREMs in the immune system and beyond. Nat. Rev. Immunol. 3, 445– 453
2. Klesney-Tait, J., Turnbull, I. R., and Colonna, M. (2006) The TREM receptor family and signal integration. Nat. Immunol. 7, 1266 –1273
3. Schmid, C. D., Sautkulis, L. N., Danielson, P. E., Cooper, J., Hasel, K. W., Hilbush, B. S., Sutcliffe, J. G., and Carson, M. J. (2002) Heterogeneous expression of the triggering receptor expressed on myeloid cells-2 on adult murine microglia. J. Neurochem. 83, 1309 –1320
4. Sessa, G., Podini, P., Mariani, M., Meroni, A., Spreafico, R., Sinigaglia, F., Colonna, M., Panina, P., and Meldolesi, J. (2004) Distribution and signaling of TREM2/DAP12, the receptor system mutated in human polycystic lipomembraneous osteodysplasia with sclerosing leukoencephalopathy dementia. Eur. J. Neurosci. 20, 2617–2628
5. Ivashkiv, L. B. (2008) A signal-switch hypothesis for cross-regulation of cytokine and TLR signalling pathways. N. Rev. Immunol. 8, 816 – 822
6. Vicente-Manzanares, M., and Sánchez-Madrid, F. (2004) Role of the cytoskeleton during leukocyte responses. Nat. Rev. Immunol. 4, 110 –122
7. Mizuno, N., Uematsu, S., and Ono, M. (1975) [Pustular psoriasis (Zum-busch) treated with 8-methoxypsoralen phototherapy (author’s transl)]. Nihon Hifuka Gakkai Zasshi 85, 587–594
8. Kondo, T., Takahashi, K., Kohara, N., Takahashi, Y., Hayashi, S., Takahashi, H., Matsuo, H., Yamazaki, M., Inoue, K., Miyamoto, K., and Yama-mura, T. (2002) Heterogeneity of presenile dementia with bone cysts (Nasu-Hakola disease): three genetic forms. Neurology 59, 1105–1107
9. Paloneva, J., Manninen, T., Christman, G., Hovanes, K., Mandelin, J., Adolfsson, R., Bianchin, M., Bird, T., Miranda, R., Salmaggi, A., Traneb-jaerg, L., Konttinen, Y., and Peltonen, L. (2002) Mutations in two genes encoding different subunits of a receptor signaling complex result in an identical disease phenotype. Am. J. Hum. Genet. 71, 656 – 662
10. Hamerman, J. A., Jarjoura, J. R., Humphrey, M. B., Nakamura, M. C., Seaman, W. E., and Lanier, L. L. (2006) Cutting edge: inhibition of TLR and FcR responses in macrophages by triggering receptor expressed on myeloid cells (TREM)-2 and DAP12. J. Immunol. 177, 2051–2055
11. Turnbull, I. R., Gilfillan, S., Cella, M., Aoshi, T., Miller, M., Piccio, L., Hernandez, M., and Colonna, M. (2006) Cutting edge: TREM-2 attenuates macrophage activation. J. Immunol. 177, 3520 –3524
12. Hamerman, J. A., Tchao, N. K., Lowell, C. A., and Lanier, L. L. (2005) Enhanced Toll-like receptor responses in the absence of signaling adaptor DAP12. Nat. Immunol. 6, 579 –586
13. Cady, J., Koval, E. D., Benitez, B. A., Zaidman, C., Jockel-Balsarotti, J., Allred, P., Baloh, R. H., Ravits, J., Simpson, E., Appel, S. H., Pestronk, A., Goate, A. M., Miller, T. M., Cruchaga, C., and Harms, M. B. (2014) TREM2 variant p.R47H as a risk factor for sporadic amyotrophic lateral sclerosis. JAMA Neurol. 71, 449 – 453
14. Guerreiro, R. J., Lohmann, E., Brás, J. M., Gibbs, J. R., Rohrer, J. D., Gurun-lian, N., Dursun, B., Bilgic, B., Hanagasi, H., Gurvit, H., Emre, M., Singleton, A., and Hardy, J. (2013) Using exome sequencing to reveal mutations in TREM2 presenting as a frontotemporal dementia-like syndrome without bone involvement. JAMA Neurol. 70, 78 – 84
15. Guerreiro, R., Wojtas, A., Bras, J., Carrasquillo, M., Rogaeva, E., Majounie, E., Cruchaga, C., Sassi, C., Kauwe, J. S., Younkin, S., Hazrati, L., Collinge, J., Pocock, J., Lashley, T., Williams, J., et al. (2013) TREM2 variants in Alzheimer’s disease. N. Engl. J. Med. 368, 117–127
16. Jonsson, T., Stefansson, H., Steinberg, S., Jonsdottir, I., Jonsson, P. V., Snaedal, J., Bjornsson, S., Huttenlocher, J., Levey, A. I., Lah, J. J., Rujescu, D., Hampel, H., Giegling, I., Andreassen, O. A., Engedal, K., et al. (2013) Variant of TREM2 associated with the risk of Alzheimer’s disease. N. Engl. J. Med. 368, 107–116
17. Rayaprolu, S., Mullen, B., Baker, M., Lynch, T., Finger, E., Seeley, W. W., Hatanpaa, K. J., Lomen-Hoerth, C., Kertesz, A., Bigio, E. H., Lippa, C., Josephs, K. A., Knopman, D. S., White, C. L., 3rd, Caselli, R., et al. (2013) TREM2 in neurodegeneration: evidence for association of the p.R47H variant with frontotemporal dementia and Parkinson’s disease. Mol. Neurodegener. 8, 19
18. Cuyvers, E., Bettens, K., Philtjens, S., Van Langenhove, T., Gijselinck, I., van der Zee, J., Engelborghs, S., Vandenbulcke, M., Van Dongen, J., Geerts, N., Maes, G., Mattheijssens, M., Peeters, K., Cras, P., Vandenberghe, R., et al. (2014) Investigating the role of rare heterozygous TREM2 variants in Alzheimer’s disease and frontotemporal dementia. Neurobiol. Aging 35, 726.e11–726.e19
19. Borroni, B., Ferrari, F., Galimberti, D., Nacmias, B., Barone, C., Bagnoli, S., Fenoglio, C., Piaceri, I., Archetti, S., Bonvicini, C., Gennarelli, M., Turla, M., Scarpini, E., Sorbi, S., and Padovani, A. (2014) Heterozygous TREM2 mutations in frontotemporal dementia. Neurobiol. Aging 35, 934.e7–934.e10
20. Kleinberger, G., Yamanishi, Y., Suárez-Calvet, M., Czirr, E., Lohmann, E., Cuyvers, E., Struyfs, H., Pettkus, N., Wenninger-Weinzierl, A., Mazaheri, F., Tahirovic, S., Lleó, A., Alcolea, D., Fortea, J., Willem, M., et al. (2014) TREM2 mutations implicated in neurodegeneration impair cell surface transport and phagocytosis. Sci. Transl. Med. 6, 243ra86
21. Piccio, L., Deming, Y., Del-Águila, J. L., Ghezzi, L., Holtzman, D. M., Fa-gan, A. M., Fenoglio, C., Galimberti, D., Borroni, B., and Cruchaga, C. (2016) Cerebrospinal fluid soluble TREM2 is higher in Alzheimer disease and associated with mutation status. Acta Neuropathol. 131, 925–933
22. Heslegrave, A., Heywood, W., Paterson, R., Magdalinou, N., Svensson, J., Johansson, P., Öhrfelt, A., Blennow, K., Hardy, J., Schott, J., Mills, K., and Zetterberg, H. (2016) Increased cerebrospinal fluid soluble TREM2 concentration in Alzheimer’s disease. Mol. Neurodegener. 11, 3
23. Jay, T. R., Miller, C. M., Cheng, P. J., Graham, L. C., Bemiller, S., Broihier, M. L., Xu, G., Margevicius, D., Karlo, J. C., Sousa, G. L., Cotleur, A. C., Butovsky, O., Bekris, L., Staugaitis, S. M., Leverenz, J. B., et al. (2015) TREM2 deficiency eliminates TREM2 inflammatory macrophages and ameliorates pathology in Alzheimer’s disease mouse models. J. Exp. Med. 212, 287–295
24. Wang, Y., Cella, M., Mallinson, K., Ulrich, J. D., Young, K. L., Robinette, M. L., Gilfillan, S., Krishnan, G. M., Sudhakar, S., Zinselmeyer, B. H., Holtzman, D. M., Cirrito, J. R., and Colonna, M. (2015) TREM2 lipid sensing sustains the microglial response in an Alzheimer’s disease model. Cell 160, 1061–1071
25. Paulmurugan, R., and Gambhir, S. S. (2003) Monitoring protein-protein interactions using split synthetic Renilla luciferase protein-fragment-assisted complementation. Anal. Chem. 75, 1584 –1589
26. Fujikawa, Y., and Kato, N. (2007) Split luciferase complementation assay to study protein-protein interactions in Arabidopsis protoplasts. Plant J. 52, 185–195
27. Deng, Q., Wang, D., Xiang, X., Gao, X., Hardwidge, P. R., Kaushik, R. S., Wolff, T., Chakravarty, S., and Li, F. (2011) Application of a split luciferase complementation assay for the detection of viral protein-protein interactions. J. Virol. Methods 176, 108 –111
28. Matthews, J. C., Hori, K., and Cormier, M. J. (1977) Purification and properties of Renilla reniformis luciferase. Biochemistry 16, 85–91
29. Takahashi, K., Prinz, M., Stagi, M., Chechneva, O., and Neumann, H. (2007) TREM2-transduced myeloid precursors mediate nervous tissue debris clearance and facilitate recovery in an animal model of multiple sclerosis. PLoS Med. 4, e124
30. Frank, S., Burbach, G. J., Bonin, M., Walter, M., Streit, W., Bechmann, I., and Deller, T. (2008) TREM2 is upregulated in amyloid plaque-associated microglia in aged APP23 transgenic mice. Glia 56, 1438 –1447
31. Bouchon, A., Hernández-Munain, C., Cella, M., and Colonna, M. (2001) A DAP12-mediated pathway regulates expression of CC chemokine receptor 7 and maturation of human dendritic cells. J. Exp. Med. 194, 1111–1122
32. Peng, Q., Malhotra, S., Torchia, J. A., Kerr, W. G., Coggeshall, K. M., and Humphrey, M. B. (2010) TREM2- and DAP12-dependent activation of PI3K requires DAP10 and is inhibited by SHIP1. Sci. Signal. 3, ra38
33. Hsieh, C. L., Koike, M., Spusta, S. C., Niemi, E. C., Yenari, M., Nakamura, M. C., and Seaman, W. E. (2009) A role for TREM2 ligands in the phagocytosis of apoptotic neuronal cells by microglia. J. Neurochem. 109, 1144 –1156
34. Zhong, L., Chen, X. F., Zhang, Z. L., Wang, Z., Shi, X. Z., Xu, K., Zhang, Y. W., Xu, H., and Bu, G. (2015) DAP12 stabilizes the C-terminal fragment of the triggering receptor expressed on myeloid cells-2 (TREM2) and protects against LPS-induced pro-inflammatory response. J. Biol. Chem. 290, 15866 –15877
35. Takahashi, K., Rochford, C. D., and Neumann, H. (2005) Clearance of apoptotic neurons without inflammation by microglial triggering receptor expressed on myeloid cells-2. J. Exp. Med. 201, 647– 657
36. Melchior, B., Garcia, A. E., Hsiung, B. K., Lo, K. M., Doose, J. M., Thrash, J. C., Stalder, A. K., Staufenbiel, M., Neumann, H., and Carson, M. J. (2010) Dual induction of TREM2 and tolerance-related transcript, Tmem176b, in amyloid transgenic mice: implications for vaccine-based therapies for Alzheimer’s disease. ASN Neuro 2, e00037
37. Yuan, P., Condello, C., Keene, C. D., Wang, Y., Bird, T. D., Paul, S. M., Luo, W., Colonna, M., Baddeley, D., and Grutzendler, J. (2016) TREM2 haplodeficiency in mice and humans impairs the microglia barrier function leading to decreased amyloid compaction and severe axonal dystrophy. Neuron 90, 724 –739
38. Jiang, T., Tan, L., Zhu, X. C., Zhang, Q. Q., Cao, L., Tan, M. S., Gu, L. Z., Wang, H. F., Ding, Z. Z., Zhang, Y. D., and Yu, J. T. (2014) Upregulation of TREM2 ameliorates neuropathology and rescues spatial cognitive impairment in a transgenic mouse model of Alzheimer’s disease. Neuropsycho-pharmacology 39, 2949 –2962
39. Yeh, F. L., Wang, Y., Tom, I., Gonzalez, L. C., and Sheng, M. (2016) TREM2 binds to apolipoproteins, including APOE and CLU/APOJ, and thereby facilitates uptake of amyloid- by microglia. Neuron 91, 328 –340
40. Atagi, Y., Liu, C. C., Painter, M. M., Chen, X. F., Verbeeck, C., Zheng, H., Li, X., Rademakers, R., Kang, S. S., Xu, H., Younkin, S., Das, P., Fryer, J. D., and Bu, G. (2015) Apolipoprotein E is a ligand for triggering receptor expressed on myeloid cells 2 (TREM2). J. Biol. Chem. 290, 26043–26050
41. Fuller, A. D., and Van Eldik, L. J. (2008) MFG-E8 regulates microglial phagocytosis of apoptotic neurons. J. Neuroimmune Pharmacol. 3, 246–256
42. Liu, Y., Yang, X., Guo, C., Nie, P., Liu, Y., and Ma, J. (2013) Essential role of MFG-E8 for phagocytic properties of microglial cells. PLoS One 8, e55754
43. Hanayama, R., Tanaka, M., Miwa, K., Shinohara, A., Iwamatsu, A., and Nagata, S. (2002) Identification of a factor that links apoptotic cells to phagocytes. Nature 417, 182–187
44. Lew, E. D., Oh, J., Burrola, P. G., Lax, I., Zagorska, A., Traves, P. G., Sch-lessinger, J., and Lemke, G. (2014) Differential TAM receptor-ligand-phospholipid interactions delimit differential TAM bioactivities. Elife 3, e03385
45. Tsou, W. I., Nguyen, K. Q., Calarese, D. A., Garforth, S. J., Antes, A. L., Smirnov, S. V., Almo, S. C., Birge, R. B., and Kotenko, S. V. (2014) Receptor tyrosine kinases, TYRO3, AXL, and MER, demonstrate distinct patterns and complex regulation of ligand-induced activation. J. Biol. Chem. 289, 25750 –25763
46. van der Meer, J. H., van der Poll, T., and van’t Veer, C. (2014) TAM receptors, Gas6, and protein S: roles in inflammation and hemostasis. Blood 123, 2460 –2469
47. N’Diaye, E. N., Branda, C. S., Branda, S. S., Nevarez, L., Colonna, M., Lowell, C., Hamerman, J. A., and Seaman, W. E. (2009) TREM-2 (triggering receptor expressed on myeloid cells 2) is a phagocytic receptor for bacteria. J. Cell Biol. 184, 215–223
48. Bianchin, M. M., Capella, H. M., Chaves, D. L., Steindel, M., Grisard, E. C., Ganev, G. G., da Silva Júnior, J. P., Neto Evaldo, S., Poffo, M. A., Walz, R., Carlotti Júnior, C. G., and Sakamoto, A. C. (2004) Nasu-Hakola disease (polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy—PLOSL): a dementia associated with bone cystic lesions. From clinical to genetic and molecular aspects. Cell. Mol. Neurobiol. 24, 1–24
49. Song, W., Hooli, B., Mullin, K., Jin, S. C., Cella, M., Ulland, T. K., Wang, Y., Tanzi, R. E, and Colonna, M. (2017) Alzheimer’s disease-associated TREM2 variants exhibit either decreased or increased ligand-dependent activation. Alzheimers Dement. 13, 381–387
50. Rizvi, S. M., and Raghavan, M. (2010) Mechanisms of function of tapasin, a critical major histocompatibility complex class I assembly factor. Traffic 11, 332–347
51. Daws, M. R., Lanier, L. L., Seaman, W. E., and Ryan, J. C. (2001) Cloning and characterization of a novel mouse myeloid DAP12-associated receptor family. Eur. J. Immunol. 31, 783–791
52. Iqbal, K., Alonso, A. C., Gong, C. X., Khatoon, S., Pei, J. J., Wang, J. Z., and Grundke-Iqbal, I. (1998) Mechanisms of neurofibrillary degeneration and the formation of neurofibrillary tangles. J. Neural. Transm. Suppl. 53, 169 –180