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TY - JOUR AU - Takegahara, Noriko AU - Takamatsu, Hyota AU - Toyofuku, Toshihiko AU - Tsujimura, Tohru AU - Okuno, Tatsusada AU - Yukawa, Kazunori AU - Mizui, Masayuki AU - Yamamoto, Midori AU - Prasad, Durbaka V.R. AU - Suzuki, Kazuhiro AU - Ishii, Masaru AU - Terai, Kenta AU - Moriya, Masayuki AU - Nakatsuji, Yuji AU - Sakoda, Saburo AU - Sato, Shintaro AU - Akira, Shizuo AU - Takeda, Kiyoshi AU - Inui, Masanori AU - Takai, Toshiyuki AU - Ikawa, Masahito AU - Okabe, Masaru AU - Kumanogoh, Atsushi AU - Kikutani, Hitoshi PY - 2006 DA - 2006/06/01 TI - Plexin-A1 and its interaction with DAP12 in immune responses and bone homeostasis JO - Nature Cell Biology SP - 615 EP - 622 VL - 8 IS - 6 AB - Semaphorins and their receptors have diverse functions in axon guidance, organogenesis, vascularization and/or angiogenesis, oncogenesis and regulation of immune responses1,2,3,4,5,6,7,8,9,10,11. The primary receptors for semaphorins are members of the plexin family2,12,13,14. In particular, plexin-A1, together with ligand-binding neuropilins, transduces repulsive axon guidance signals for soluble class III semaphorins15, whereas plexin-A1 has multiple functions in chick cardiogenesis as a receptor for the transmembrane semaphorin, Sema6D, independent of neuropilins16. Additionally, plexin-A1 has been implicated in dendritic cell function in the immune system17. However, the role of plexin-A1 in vivo, and the mechanisms underlying its pleiotropic functions, remain unclear. Here, we generated plexin-A1-deficient (plexin-A1−/−) mice and identified its important roles, not only in immune responses, but also in bone homeostasis. Furthermore, we show that plexin-A1 associates with the triggering receptor expressed on myeloid cells-2 (Trem-2), linking semaphorin-signalling to the immuno-receptor tyrosine-based activation motif (ITAM)-bearing adaptor protein, DAP12. These findings reveal an unexpected role for plexin-A1 and present a novel signalling mechanism for exerting the pleiotropic functions of semaphorins. SN - 1476-4679 UR - https://doi.org/10.1038/ncb1416 DO - 10.1038/ncb1416 ID - Takegahara2006 ER -