Osteopetrosis and thalamic hypomyelinosis with synaptic degeneration in DAP12-deficient mice

Kaifu, Tomonori; Nakahara, Jin; Inui, Makoto; Mishima, Kenichi; Momiyama, Toshihiko; Kaji, Mitsuji; Sugahara, Akiko; Koito, Hisami; Ujike-Asai, Azusa; Nakamura, Akira; Kanazawa, Kiyoshi; Tan-Takeuchi, Kyoko; Iwasaki, Katsunori; Yokoyama, Wayne M.; Kudo, Akira; Fujiwara, Michihiro; Asou, Hiroaki; Takai, Toshiyuki

doi:10.1172/jci16923

Cited by 304 publications

(270 citation statements)

References 40 publications

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“…Thus, although many receptors utilize DAP12 as an adaptor molecule for cell signaling, at least some functions of TREM-2 are not redundant in function with other DAP12-associated receptors. TREM-2-deficient mice have not yet been described, but mice deficient in DAP12 have been studied, and they also show changes in brain and bone (10). Although TREM-2 binds to bacteria, neither humans nor mice deficient in TREM-2 are known to have increased susceptibility to bacterial infection.…”

Section: Discussionmentioning

confidence: 99%

“…Humans deficient in TREM-2 develop degenerative brain disease and bone cysts (8), a clinical presentation that is similar if not identical to humans lacking DAP12 (9). Less dramatic changes in brain and bone have also been described in DAP12-deficient mice (10), which also accumulate dendritic (Langerhans) cells in the skin (11), and are resistant to experimental autoimmune encephalitis (12). Thus, TREM-2 is important in maintenance of the normal architecture of bone and brain.…”

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confidence: 97%

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Pattern Recognition by TREM-2: Binding of Anionic Ligands

Daws

Sullam

Niemi³

et al. 2003

The Journal of Immunology

247

233

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We recently described the cloning of murine triggering receptor expressed by myeloid cells (TREM) 2, a single Ig domain DNAX adaptor protein 12-associated receptor expressed by cells of the myeloid lineage. In this study, we describe the identification of ligands for TREM-2 on both bacteria and mammalian cells. First, by using a TREM-2A/IgG1-Fc fusion protein, we demonstrate specific binding to a number of Gram-negative and Gram-positive bacteria and to yeast. Furthermore, we show that fluorescently labeled Escherichia coli and Staphylococcus aureus bind specifically to TREM-2-transfected cells. The binding of TREM-2A/Ig fusion protein to E. coli can be inhibited by the bacterial products LPS, lipoteichoic acid, and peptidoglycan. Additionally, binding can be inhibited by a number of other anionic carbohydrate molecules, including dextran sulfate, suggesting that ligand recognition is based partly on charge. Using a sensitive reporter assay, we demonstrate activation of a TREM-2A/CD3ζ chimeric receptor by both bacteria and dextran sulfate. Finally, we demonstrate binding of TREM-2A/Ig fusion to a series of human astrocytoma lines but not to a variety of other cell lines. The binding to astrocytomas, like binding to bacteria, is inhibited by anionic bacterial products, suggesting either a similar charge-based ligand recognition method or overlapping binding sites for recognition of self- and pathogen-expressed ligands.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 97%

Pattern Recognition by TREM-2: Binding of Anionic Ligands

Daws

Sullam

Niemi³

et al. 2003

The Journal of Immunology

247

233

View full text Add to dashboard Cite

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“…only develop osteopetrosis 20,60,61 but also are resistant to EAE. 62 Interestingly, genetic mutations in human DAP12 or TREM-2 result in a bone-fracture syndrome called Nasu-Hakola disease, further suggesting that plexin-A1 physiologically associates with the TREM/ DAP12 complex and that this interaction is relevant to these diseases.…”

Section: Regulation Of Immune Cell Responses H Takamatsu Et Al 85mentioning

confidence: 99%

Regulation of immune cell responses by semaphorins and their receptors

2010

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Semaphorins were originally identified as axon guidance factors involved in the development of the neuronal system. However, accumulating evidence indicates that several members of semaphorins, so-called 'immune semaphorins', are crucially involved in various phases of immune responses. These semaphorins regulate both immune cell interactions and immune cell trafficking during physiological and pathological immune responses. Here, we review the following two functional aspects of semaphorins and their receptors in immune responses: their functions in cell-cell interactions and their involvement in immune cell trafficking.

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“…Vav1 Ϫ/Ϫ and DAP12 Ϫ/Ϫ mice have been described elsewhere and were bred to generate Vav1 Ϫ/Ϫ DAP12 Ϫ/Ϫ double knockout mice (F6 on C57BL/6 background) (23,24). Splenic NK cells were purified by positive selection with anti-DX-5 microbeads (Miltenyi Biotec), according to the manufacturer's recommendation.…”

Section: Mice and Nk Cell Purificationmentioning

confidence: 99%

Vav1 Controls DAP10-Mediated Natural Cytotoxicity by Regulating Actin and Microtubule Dynamics

Graham

Cella

Giurisato

et al. 2006

The Journal of Immunology

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The NK cell-activating receptor NKG2D recognizes several MHC class I-related molecules expressed on virally infected and tumor cells. Human NKG2D transduces activation signals exclusively via an associated DAP10 adaptor containing a YxNM motif, whereas murine NKG2D can signal through either DAP10 or the DAP12 adaptor, which contains an ITAM sequence. DAP10 signaling is thought to be mediated, at least in part, by PI3K and is independent of Syk/Zap-70 kinases; however, the exact mechanism by which DAP10 induces natural cytotoxicity is incompletely understood. Herein, we identify Vav1, a Rho GTPase guanine nucleotide exchange factor, as a critical signaling mediator downstream of DAP10 in NK cells. Specifically, using mice deficient in Vav1 and DAP12, we demonstrate an essential role for Vav1 in DAP10-induced NK cell cytoskeletal polarization involving both actin and microtubule networks, maturation of the cytolytic synapse, and target cell lysis. Mechanistically, we show that Vav1 interacts with DAP10 YxNM motifs through the adaptor protein Grb2 and is required for activation of PI3K-dependent Akt signaling. Based on these findings, we propose a novel model of ITAM-independent signaling by Vav downstream of DAP10 in NK cells.

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Osteopetrosis and thalamic hypomyelinosis with synaptic degeneration in DAP12-deficient mice

Cited by 304 publications

References 40 publications

Pattern Recognition by TREM-2: Binding of Anionic Ligands

Pattern Recognition by TREM-2: Binding of Anionic Ligands

Regulation of immune cell responses by semaphorins and their receptors

Vav1 Controls DAP10-Mediated Natural Cytotoxicity by Regulating Actin and Microtubule Dynamics

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