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

Noriko Takegahara, Hyota Takamatsu, Toshihiko Toyofuku, Tohru Tsujimura, Tatsusada Okuno, Kazunori Yukawa, Masayuki Mizui, Midori Yamamoto, Durbaka V.R. Prasad, Kazuhiro Suzuki, Masaru Ishii, Kenta Terai, Masayuki Moriya, Yuji Nakatsuji, Saburo Sakoda, Shintaro Sato, Shizuo Akira, Kiyoshi Takeda, Masanori Inui, Toshiyuki TakaiMasahito Ikawa, Masaru Okabe, Atsushi Kumanogoh, Hitoshi Kikutani

Research output: Contribution to journalArticlepeer-review

212 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)615-622
Number of pages8
JournalNature Cell Biology
Issue number6
Publication statusPublished - 2006 Jun


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