The TREM2-DAP12 signaling pathway in Nasu–Hakola disease: a molecular genetics perspective

References

• Nasu TTY, Terayama K. A lipid metabolic disease – “membranous lipodystrophy” – an autopsy case demonstrating numerous peculiar membrane-structures composed of compound lipid in bone and bone marrow and various adipose tissues. Pathol Int. 1973;23:539–558.
   Google Scholar
• Hakola H. Neuropsychiatric and genetic aspects of a new hereditary disease characterized by progressive dementia and lipomembranous polycystic osteodysplasia. Acta Psychiatr Scand Suppl. 1972;232(1):1–173.
   Google Scholar
• Paloneva J, Autti T, Raininko R, et al. CNS manifestations of Nasu-Hakola disease: a frontal dementia with bone cysts. Neurology. 2001;56:1552–1558.
   PubMed Web of Science ®Google Scholar
• Kaneko M, Sano K, Nakayama J, Amano N. Nasu-Hakola disease: the first case reported by Nasu and review. Neuropathology. 2010;30:463–470.
   PubMed Web of Science ®Google Scholar
• Kilic SA, Oner AY, Yuce C, Ozlu IC. Imaging findings of Nasu-Hakola disease: a case report. Clin Imaging. 2012;36:877–880.
   Web of Science ®Google Scholar
• Madry H, Prudlo J, Grgic A, Freyschmidt J. Nasu-Hakola disease (PLOSL) report of five cases and review of the literature. Clin Orthop Relat Res. 2006;454:262–269.
   Google Scholar
• Bianchin MM, Capella HM, Chaves DL, et al. 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. 2004;24(1):1–24.
   PubMed Web of Science ®Google Scholar
• Al-Brahim N, Ceballos K, Sur M, Daya D, Alowami S. Lipomembranous panniculitis: report of a case. Ann Diagn Pathol. 2007;11(4):282–284.
   Web of Science ®Google Scholar
• Bilgic B, Gelisin O, Guerreiro R, et al. Neuroimaging findings of Nasu-Hakola disease. Alzheimer Dement. 2014;10(4 Suppl):2415.
   Google Scholar
• Ueki Y, Kohara N, Oga T, et al. Membranous lipodystrophy presenting with palilalia: a PET study of cerebral glucose metabolism. Acta Neurol Scand. 2000;102(1):60–64.
   Web of Science ®Google Scholar
• Kalimo H, Sourander P, Jarvi O, Hakola P. Vascular changes and blood-brain barrier damage in the pathogenesis of polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (membranous lipodystrophy). Acta Neurol Scand. 1994;89(5):353–361.
   PubMed Web of Science ®Google Scholar
• Paloneva J, Kestilä M, Wu J, et al. Loss-of-function mutations in TYROBP (DAP12) result in a presenile dementia with bone cysts. Nat Genet. 2000;25(3):357–361.
   PubMed Web of Science ®Google Scholar
• Paloneva J, Manninen T, Christman G, et al. Mutations in two genes encoding different subunits of a receptor signaling complex result in an identical disease phenotype. Am J Hum Genet. 2002;71(3):656–662.
   PubMed Web of Science ®Google Scholar
• Lanier LL, Corliss BC, Wu J, Leong C, Phillips JH. Immunoreceptor DAP12 bearing a tyrosine-based activation motif is involved in activating NK cells. Nature. 1998;391(6668):703–707.
   PubMed Web of Science ®Google Scholar
• Daws MR, Lanier LL, Seaman WE, Ryan JC. Cloning and characterization of a novel mouse myeloid DAP12-associated receptor family. Eur J Immunol. 2001;31(3):783–791.
   PubMed Web of Science ®Google Scholar
• Call ME, Wucherpfennig KW, Chou JJ. The structural basis for intramembrane assembly of an activating immunoreceptor complex. Nat Immunol. 2010;11(11):1023–1029.
   PubMed Web of Science ®Google Scholar
• Lanier LL. DAP10- and DAP12-associated receptors in innate immunity. Immunol Rev. 2009;227(1):150–160.
   PubMedGoogle Scholar
• Kondo T, Takahashi K, Kohara N, et al. Heterogeneity of presenile dementia with bone cysts (Nasu-Hakola disease): three genetic forms. Neurology. 2002;59(7):1105–1107.
   Web of Science ®Google Scholar
• Kuroda R, Satoh J, Yamamura T, et al. A novel compound heterozygous mutation in the DAP12 gene in a patient with Nasu-Hakola disease. J Neurol Sci. 2007;252(1):88–91.
   Web of Science ®Google Scholar
• Baeta E, Guarda C, Mendes I, et al. Síndroma Nasu-Hakola: um caso português. [Nasu- Hakola syndrome: a Portuguese case]. Sinapse. 2002;2:15–18. Portugese.
   Google Scholar
• Klunemann HH, Ridha BH, Magy L, et al. The genetic causes of basal ganglia calcification, dementia, and bone cysts: DAP12 and TREM2. Neurology. 2005;64(9):1502–1507.
   PubMed Web of Science ®Google Scholar
• Soragna D, Papi L, Ratti MT, Sestini R, Tupler R, Montalbetti L. An Italian family affected by Nasu-Hakola disease with a novel genetic mutation in the TREM2 gene. J Neurol Neurosurg Psychiatry. 2003;74(6):825–826.
   PubMed Web of Science ®Google Scholar
• Angelini DF, Zambello R, Galandrini R, et al. NKG2A inhibits NKG2C effector functions of gammadelta T cells: implications in health and disease. J Leukoc Biol. 2011;89(1):75–84.
   Web of Science ®Google Scholar
• Nakano-Yokomizo T, Tahara-Hanaoka S, Nakahashi-Oda C, et al. The immunoreceptor adapter protein DAP12 suppresses B lymphocyte-driven adaptive immune responses. J Exp Med. 2011;208(8):1661–1671.
   Web of Science ®Google Scholar
• Long CL, Humphrey MB. Osteoimmunology: the expanding role of immunoreceptors in osteoclasts and bone remodeling. Bonekey Rep. 2012;1:59.
   Google Scholar
• Paloneva J, Mandelin J, Kiialainen A, et al. DAP12/TREM2 deficiency results in impaired osteoclast differentiation and osteoporotic features. J Exp Med. 2003;198(4):669–675.
   PubMed Web of Science ®Google Scholar
• Schmid CD, Sautkulis LN, Danielson PE, et al. Heterogeneous expression of the triggering receptor expressed on myeloid cells-2 on adult murine microglia. J Neurochem. 2002;83(6):1309–1320.
   PubMed Web of Science ®Google Scholar
• Forabosco P, Ramasamy A, Trabzuni D, et al. Insights into TREM2 biology by network analysis of human brain gene expression data. Neurobiol Aging. 2013;34(12):2699–2714.
   Web of Science ®Google Scholar
• Lue LF, Schmitz C, Walker DG. What happens to microglial TREM2 in Alzheimer’s disease: immunoregulatory turned into immunopathogenic? Neuroscience. Epub 2014 Sept 5.
   Google Scholar
• Lue LF, Schmitz CT, Serrano G, Sue LI, Beach TG, Walker DG. TREM2 protein expression changes correlate with Alzheimer’s disease neurodegenerative pathologies in post-mortem temporal cortices. Brain Pathol. Epub 2014 Sep 3.
   Google Scholar
• Kaifu T, Nakahara J, Inui M, et al. Osteopetrosis and thalamic hypomyelinosis with synaptic degeneration in DAP12-deficient mice. J Clin Invest. 2003;111(3):323–332.
   PubMed Web of Science ®Google Scholar
• Kiialainen A, Hovanes K, Paloneva J, Kopra O, Peltonen L. Dap12 and Trem2, molecules involved in innate immunity and neurodegeneration, are co-expressed in the CNS. Neurobiol Dis. 2005;18(2):314–322.
   PubMed Web of Science ®Google Scholar
• Sessa G, Podini P, Mariani M, et al. Distribution and signaling of TREM2/DAP12, the receptor system mutated in human polycystic lipomembraneous osteodysplasia with sclerosing leukoencephalopathy dementia. Eur J Neurosci. 2004;20(10):2617–2628.
   PubMed Web of Science ®Google Scholar
• Stefano L, Racchetti G, Bianco F, et al. The surface-exposed chaperone, Hsp60, is an agonist of the microglial TREM2 receptor. J Neurochem. 2009;110(1):284–294.
   PubMed Web of Science ®Google Scholar
• Lanier LL, Bakker AB. The ITAM-bearing transmembrane adaptor DAP12 in lymphoid and myeloid cell function. Immunol Today. 2000;21(12):611–614.
   Google Scholar
• Humphrey MB, Lanier LL, Nakamura MC. Role of ITAM-containing adapter proteins and their receptors in the immune system and bone. Immunol Rev. 2005;208:50–65.
   PubMed Web of Science ®Google Scholar
• Furlong MT, Mahrenholz AM, Kim KH, Ashendel CL, Harrison ML, Geahlen RL. Identification of the major sites of autophosphorylation of the murine protein-tyrosine kinase Syk. Biochim Biophys Acta. 1997;1355(2):177–190.
   Web of Science ®Google Scholar
• Peng Q, Malhotra S, Torchia JA, Kerr WG, Coggeshall KM, Humphrey MB. TREM2- and DAP12-dependent activation of PI3K requires DAP10 and is inhibited by SHIP1. Sci Signal. 2010;3(122):ra38.
   Google Scholar
• Charles JF, Humphrey MB, Zhao X, et al. The innate immune response to Salmonella enterica serovar typhimurium by macrophages is dependent on TREM2-DAP12. Infect Immun. 2008;76(6):2439–2447.
   PubMed Web of Science ®Google Scholar
• Peng Q, Long CL, Malhotra S, Humphrey MB. A physical interaction between the adaptor proteins DOK3 and DAP12 is required to inhibit lipopolysaccharide signaling in macrophages. Sci Signal. 2013;6(289):ra72.
   Web of Science ®Google Scholar
• Lupher ML Jr, Rao N, Lill NL, et al. Cbl-mediated negative regulation of the Syk tyrosine kinase. A critical role for Cbl phosphotyrosine-binding domain binding to Syk phosphotyrosine 323. J Biol Chem. 1998;273(52):35273–35281.
   PubMed Web of Science ®Google Scholar
• Otero K, Turnbull IR, Poliani PL, et al. Macrophage colony-stimulating factor induces the proliferation and survival of macrophages via a pathway involving DAP12 and beta-catenin. Nat Immunol. 2009;10(7):734–743.
   Web of Science ®Google Scholar
• Faccio R, Zou W, Colaianni G, Teitelbaum SL, Ross FP. High dose M-CSF partially rescues the Dap12-/- osteoclast phenotype. J Cell Biochem. 2003;90(5):871–883.
   Web of Science ®Google Scholar
• Mocsai A, Abram CL, Jakus Z, Hu Y, Lanier LL, Lowell CA. Integrin signaling in neutrophils and macrophages uses adaptors containing immunoreceptor tyrosine-based activation motifs. Nat Immunol. 2006;7(12):1326–1333.
   Web of Science ®Google Scholar
• Zou W, Kitaura H, Reeve J, et al. Syk, c-Src, the alphavbeta3 integrin, and ITAM immunoreceptors, in concert, regulate osteoclastic bone resorption. J Cell Biol. 2007;176(6):877–888.
   Web of Science ®Google Scholar
• Kleinberger G, Yamanishi Y, Suárez-Calvet M, et al. TREM2 mutations implicated in neurodegeneration impair cell surface transport and phagocytosis. Sci Transl Med. 2014;6(243):243ra286.
   Web of Science ®Google Scholar
• Prada I, Ongania GN, Buonsanti C, Panina-Bordignon P, Meldolesi J. Triggering receptor expressed in myeloid cells 2 (TREM2) trafficking in microglial cells: continuous shuttling to and from the plasma membrane regulated by cell stimulation. Neuroscience. 2006;140(4):1139–1148.
   PubMed Web of Science ®Google Scholar
• Wunderlich P, Glebov K, Kemmerling N, Tien NT, Neumann H, Walter J. Sequential proteolytic processing of the triggering receptor expressed on myeloid cells-2 (TREM2) protein by ectodomain shedding and gamma-secretase-dependent intramembranous cleavage. J Biol Chem. 2013;288(46):33027–33036.
   PubMed Web of Science ®Google Scholar
• Park JS, Ji IJ, An HJ, et al. Disease-associated mutations of TREM2 alter the processing of N-linked oligosaccharides in the Golgi apparatus. Traffic. 2015.
   Web of Science ®Google Scholar
• Piccio L, Buonsanti C, Cella M, et al. Identification of soluble TREM-2 in the cerebrospinal fluid and its association with multiple sclerosis and CNS inflammation. Brain. 2008;131(pt 11):3081–3091.
   PubMedGoogle Scholar
• Tomasello E, Vivier E. KARAP/DAP12/TYROBP: three names and a multiplicity of biological functions. Eur J Immunol. 2005;35(6):1670–1677.
   PubMed Web of Science ®Google Scholar
• Hsieh CL, Koike M, Spusta SC, et al. A role for TREM2 ligands in the phagocytosis of apoptotic neuronal cells by microglia. J Neurochem. 2009;109(4):1144–1156.
   PubMed Web of Science ®Google Scholar
• Colonna M. DAP12 signaling: from immune cells to bone modeling and brain myelination. J Clin Invest. 2003;111(3):313–314.
   Web of Science ®Google Scholar
• Takahashi K, Rochford CD, Neumann H. Clearance of apoptotic neurons without inflammation by microglial triggering receptor expressed on myeloid cells-2. J Exp Med. 2005;201(4):647–657.
   PubMed Web of Science ®Google Scholar
• Otero K, Shinohara M, Zhao H, et al. TREM2 and beta-catenin regulate bone homeostasis by controlling the rate of osteoclastogenesis. J Immunol. 2012;188(6):2612–2621.
   PubMed Web of Science ®Google Scholar
• Humphrey MB, Ogasawara K, Yao W, et al. The signaling adapter protein DAP12 regulates multinucleation during osteoclast development. J Bone Miner Res. 2004;19(2):224–234.
   Web of Science ®Google Scholar
• Nataf S, Anginot A, Vuaillat C, et al. Brain and bone damage in KARAP/DAP12 loss-of-function mice correlate with alterations in microglia and osteoclast lineages. Am J Pathol. 2005;166(1):275–286.
   PubMed Web of Science ®Google Scholar
• Humphrey MB, Daws MR, Spusta SC, et al. TREM2, a DAP12-associated receptor, regulates osteoclast differentiation and function. J Bone Miner Res. 2006;21(2):237–245.
   PubMed Web of Science ®Google Scholar
• Turnbull IR, Gilfillan S, Cella M, et al. Cutting edge: TREM-2 attenuates macrophage activation. J Immunol. 2006;177(6):3520–3524.
   PubMed Web of Science ®Google Scholar
• Bouchon A, Hernandez-Munain C, Cella M, Colonna MA. DAP12-mediated pathway regulates expression of CC chemokine receptor 7 and maturation of human dendritic cells. J Exp Med. 2001;194(8):1111–1122.
   PubMed Web of Science ®Google Scholar
• Hamerman JA, Tchao NK, Lowell CA, Lanier LL. Enhanced Toll-like receptor responses in the absence of signaling adaptor DAP12. Nat Immunol. 2005;6(6):579–586.
   PubMed Web of Science ®Google Scholar
• Hamerman JA, Jarjoura JR, Humphrey MB, Nakamura MC, Seaman WE, Lanier LL. Cutting edge: inhibition of TLR and FcR responses in macrophages by triggering receptor expressed on myeloid cells (TREM)-2 and DAP12. J Immunol. 2006;177(4):2051–2055.
   PubMed Web of Science ®Google Scholar
• Ito H, Hamerman JA. TREM-2, triggering receptor expressed on myeloid cell-2, negatively regulates TLR responses in dendritic cells. Eur J Immunol. 2012;42(1):176–185.
   PubMed Web of Science ®Google Scholar
• Daws MR, Sullam PM, Niemi EC, Chen TT, Tchao NK, Seaman WE. Pattern recognition by TREM-2: binding of anionic ligands. J Immunol. 2003;171(2):594–599.
   PubMed Web of Science ®Google Scholar
• N’Diaye EN, Branda CS, Branda SS, et al. TREM-2 (triggering receptor expressed on myeloid cells 2) is a phagocytic receptor for bacteria. J Cell Biol. 2009;184(2):215–223.
   PubMed Web of Science ®Google Scholar
• Ohashi K, Burkart V, Flohe S, Kolb H. Cutting edge: heat shock protein 60 is a putative endogenous ligand of the Toll-like receptor-4 complex. J Immunol. 2000;164(2):558–561.
   PubMed Web of Science ®Google Scholar
• Hansen JJ, D&#252rr A, Cournu-Rebeix I, et al. Hereditary spastic paraplegia SPG13 is associated with a mutation in the gene encoding the mitochondrial chaperonin Hsp60. Am J Hum Genet. 2002;70(5):1328–1332.
   PubMed Web of Science ®Google Scholar
• Bross P, Li Z, Hansen J, et al. Single-nucleotide variations in the genes encoding the mitochondrial Hsp60/Hsp10 chaperone system and their disease-causing potential. J Hum Genet. 2007;52(1):56–65.
   Web of Science ®Google Scholar
• Magen D, Georgopoulos C, Bross P, et al. Mitochondrial hsp60 chaperonopathy causes an autosomal-recessive neurodegenerative disorder linked to brain hypomyelination and leukodystrophy. Am J Hum Genet. 2008;83(1):30–42.
   PubMed Web of Science ®Google Scholar
• Magnoni R, Palmfeldt J, Christensen JH, et al. Late onset motoneuron disorder caused by mitochondrial Hsp60 chaperone deficiency in mice. Neurobiol Dis. 2013;54:12–23.
   Web of Science ®Google Scholar
• Takegahara N, Takamatsu H, Toyofuku T, et al. Plexin-A1 and its interaction with DAP12 in immune responses and bone homeostasis. Nat Cell Biol. 2006;8(6):615–622.
   Web of Science ®Google Scholar
• Toyofuku T, Zhang H, Kumanogoh A, et al. Guidance of myocardial patterning in cardiac development by Sema6D reverse signalling. Nat Cell Biol. 2004;6(12):1204–1211.
   Web of Science ®Google Scholar
• Takamatsu H, Takegahara N, Nakagawa Y, et al. Semaphorins guide the entry of dendritic cells into the lymphatics by activating myosin II. Nat Immunol. 2010;11(7):594–600.
   PubMed Web of Science ®Google Scholar
• Satoh J, Motohashi N, Kino Y, et al. LC3, an autophagosome marker, is expressed on oligodendrocytes in Nasu-Hakola disease brains. Orphanet J Rare Dis. 2014;9:68.
   Web of Science ®Google Scholar
• Roumier A, Bëchade C, Poncer JC, et al. Impaired synaptic function in the microglial KARAP/DAP12-deficient mouse. J Neurosci. 2004;24(50):11421–11428.
   PubMed Web of Science ®Google Scholar
• Satoh J, Tabunoki H, Ishida T, et al. Phosphorylated Syk expression is enhanced in Nasu-Hakola disease brains. Neuropathology. 2012;32(2):149–157.
   Web of Science ®Google Scholar
• Jonsson T, Stefansson H, Steinberg S, et al. Variant of TREM2 associated with the risk of Alzheimer’s disease. N Engl J Med. 2013;368(2):107–116.
   PubMed Web of Science ®Google Scholar
• Rayaprolu S, Mullen B, Baker M, et al. TREM2 in neurodegeneration: evidence for association of the p.R47H variant with frontotemporal dementia and Parkinson’s disease. Mol Neurodegener. 2013;8:19.
   PubMed Web of Science ®Google Scholar
• Abduljaleel Z, Al-Allaf FA, Khan W, et al. Evidence of trem2 variant associated with triple risk of Alzheimer’s disease. PLoS One. 2014;9(3):e92648.
   PubMed Web of Science ®Google Scholar
• Jin SC, Benitez BA, Karch CM, et al. Coding variants in TREM2 increase risk for Alzheimer’s disease. Hum Mol Genet. 2014;23(21):5838–5846.
   PubMed Web of Science ®Google Scholar
• Ulrich JD, Finn MB, Wang Y, et al. Altered microglial response to Abeta plaques in APPPS1-21 mice heterozygous for TREM2. Mol Neurodegener. 2014;9:20.
   PubMed Web of Science ®Google Scholar
• Stewart CR, Stuart LM, Wilkinson K, et al. CD36 ligands promote sterile inflammation through assembly of a Toll-like receptor 4 and 6 heterodimer. Nat Immunol. 2010;11(2):155–161.
   PubMed Web of Science ®Google Scholar
• Moore KJ, El Khoury J, Medeiros LA, et al. A CD36-initiated signaling cascade mediates inflammatory effects of beta-amyloid. J Biol Chem. 2002;277(49):47373–47379.
   Web of Science ®Google Scholar
• Giuliano S, Agresta AM, De Palma A, et al. Proteomic analysis of lymphoblastoid cells from Nasu-Hakola patients: a step forward in our understanding of this neurodegenerative disorder. PLoS One. 2014;9(12):e110073.
   Web of Science ®Google Scholar
• Fujimoto S, Goda T, Mochizuki K. In vivo evidence of enhanced di-methylation of histone H3 K4 on upregulated genes in adipose tissue of diabetic db/db mice. Biochem Biophys Res Commun. 2011;404(1):223–227.
   Web of Science ®Google Scholar
• Grant RW, Vester Boler BM, Ridge TK, Graves TK, Swanson KS. Adipose tissue transcriptome changes during obesity development in female dogs. Physiol Genomics. 2011;43(6):295–307.
   Web of Science ®Google Scholar
• Park M, Yi JW, Kim EM, et al. Triggering receptor expressed on myeloid cells 2 (TREM2) promotes adipogenesis and diet-induced obesity. Diabetes. Epub 2014 Aug 11.
   Google Scholar