Cytoskeletal dysfunction dominates in DAP12-deficient osteoclasts

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Cytoskeletal dysfunction dominates in DAP12-deficient osteoclasts.

Despite evidence that DAP12 regulates osteoclasts, mice lacking the ITAM-bearing protein exhibit only mild osteopetrosis. Alternatively, Dap12(-/-) mice, also lacking FcRgamma, are severely osteopetrotic, suggesting that FcRgamma compensates for DAP12 deficiency in the bone-resorbing polykaryons. Controversy exists, however, as to whether these co-stimulatory molecules regulate differentiation ...

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Absence of Dap12 and the αvβ3 integrin causes severe osteopetrosis

In vitro, ligand occupancy of αvβ3 integrin induces phosphorylation of Dap12, which is essential for osteoclast function. Like mice deleted of only αvβ3, Dap12(-/-) mice exhibited a slight increase in bone mass, but Dap12(-/-) mice, lacking another ITAM protein, FcRγ, were severely osteopetrotic. The mechanism by which FcRγ compensates for Dap12 deficiency is unknown. We find that co-deletion o...

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TREM-2 is an immunoglobulin-like cell surface receptor associated with DAP12/KARAP that activates monocyte-derived dendritic cells (DCs) in vitro. Recently, it has been shown that genetic defects of human DAP12/KARAP and TREM-2 result in a rare syndrome characterized by bone cysts and presenile dementia called Nasu-Hakola disease. This observation suggests that TREM-2 may function in myeloid ce...

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Mice that lack the adaptor protein DAP12 defy deadly bacterial infections, according to Turnbull and colleagues on page 363. DAP12-deficient mice developed a muted inflammatory response, allowing the immune system to clear the bacteria without triggering septic shock. DAP12 is a transmembrane adaptor protein that is associated with an array of DAP12-deficient mice (dotted line) are resistant to...

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ژورنال

عنوان ژورنال: Journal of Cell Science

سال: 2010

ISSN: 1477-9137,0021-9533

DOI: 10.1242/jcs.069872