Phospholipase Cgamma2 mediates RANKL-stimulated lymph node organogenesis and osteoclastogenesis.

The Journal of Biological Chemistry
Yabing ChenDemin Wang

Abstract

Phospholipase Cgamma2 (PLCgamma2) is an important signaling effector of multiple receptors in the immune system. Here we show that PLCgamma2-deficient mice displayed impaired lymph node organogenesis but normal splenic structure and Peyer's patches. Receptor activator of NF-kappaB ligand (RANKL) is a tumor necrosis factor family cytokine and is essential for lymph node organogenesis. Importantly, PLCgamma2 deficiency severely impaired RANKL signaling, resulting in marked reduction of RANKL-induced activation of MAPKs, p38 and JNK, but not ERK. The lack of PLCgamma2 markedly diminished RANKL-induced activation of NF-kappaB, AP-1, and NFATc1. Moreover, PLCgamma2 deficiency impaired RANKL-mediated biological function, leading to failure of the PLCgamma2-deficient bone marrow macrophage precursors to differentiate into osteoclasts after RANKL stimulation. Re-introduction of PLCgamma2 but not PLCgamma1 restores RANKL-mediated osteoclast differentiation of PLCgamma2-deficient bone marrow-derived monocyte/macrophage. Taken together, PLCgamma2 is essential for RANK signaling, and its deficiency leads to defective lymph node organogenesis and osteoclast differentiation.

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Citations

Jul 14, 2011·European Journal of Clinical Investigation·Zsuzsanna KertészAttila Mócsai
Sep 15, 2010·The Journal of Biological Chemistry·Jianfeng ChenYabing Chen
Apr 8, 2011·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·George PanJay M McDonald
Mar 31, 2011·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Teruya KawamotoSteven A Lietman
Mar 22, 2012·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Jianfeng ChenYabing Chen
Mar 21, 2009·The Journal of Biological Chemistry·Naoko IrieKoichi Matsuo
Jul 9, 2020·Frontiers in Cell and Developmental Biology·Dávid S Győri, Attila Mócsai
Dec 10, 2009·Physiology·Yoshikazu Nakamura, Kiyoko Fukami
Jun 16, 2019·Cell Calcium·Lisa J RobinsonJonathan Soboloff
Jun 23, 2021·The Journal of Biological Chemistry·Jacob T JacksonSeth L Masters

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