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KMID : 0578320120330040401
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Molecules and Cells
2012 Volume.33 No. 4 p.401 ~ p.406
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The Transmembrane Adaptor Protein, Linker for Activation of T cells (LAT), Regulates RANKL-Induced Osteoclast Differentiation
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Kim Kab-Sun
Kim Jung-Ha
Moon Jang-Bae
Lee Jong-Won
Kwak Han-bok
Park Yong-Wook
Kim Nack-Sung
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Abstract
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RANKL induces the formation of osteoclasts, which are responsible for bone resorption. Herein we investigate the role of the transmembrane adaptor proteins in RANKL-induced osteoclastogenesis. LAT positively regulates osteoclast differentiation and is up-regulated by RANKL via c-Fos and NFATc1, whereas LAB and LIME act as negative modulators of osteoclastogenesis. In addition, silencing of LAT by RNA interference or overexpression of a LAT dominant negative in bone marrow-derived macrophage cells attenuates RANKL-induced osteoclast formation. Furthermore, LAT is in-volved in RANKL-induced PLC? activation and NFATc1 induction. Thus, our data suggest that LAT acts as a positive regulator of RANKL-induced osteoclastogenesis.
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KEYWORD
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gene expression, LAT, osteoclast, RANKL, transmembrane adaptor
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