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Publication : Plexin-A1 and its interaction with DAP12 in immune responses and bone homeostasis.

First Author  Takegahara N Year  2006
Journal  Nat Cell Biol Volume  8
Issue  6 Pages  615-22
PubMed ID  16715077 Mgi Jnum  J:110786
Mgi Id  MGI:3641066 Doi  10.1038/ncb1416
Citation  Takegahara N, et al. (2006) Plexin-A1 and its interaction with DAP12 in immune responses and bone homeostasis. Nat Cell Biol 8(6):615-22
abstractText  Semaphorins and their receptors have diverse functions in axon guidance, organogenesis, vascularization and/or angiogenesis, oncogenesis and regulation of immune responses. The primary receptors for semaphorins are members of the plexin family. In particular, plexin-A1, together with ligand-binding neuropilins, transduces repulsive axon guidance signals for soluble class III semaphorins, whereas plexin-A1 has multiple functions in chick cardiogenesis as a receptor for the transmembrane semaphorin, Sema6D, independent of neuropilins. Additionally, plexin-A1 has been implicated in dendritic cell function in the immune system. 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.
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