title: Plexin-A1 and its interaction with DAP12 in immune responses and bone homeostasis.
abstract: 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.
authors.affiliation: Department of Molecular Immunology and CREST program of JST, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Takegahara
authors.forename: Hyota
authors.initials: H
authors.lastname: Takamatsu
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Toyofuku
authors.forename: Tohru
authors.initials: T
authors.lastname: Tsujimura
authors.forename: Tatsusada
authors.initials: T
authors.lastname: Okuno
authors.forename: Kazunori
authors.initials: K
authors.lastname: Yukawa
authors.forename: Masayuki
authors.initials: M
authors.lastname: Mizui
authors.forename: Midori
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Durbaka V R
authors.initials: DV
authors.lastname: Prasad
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Suzuki
authors.forename: Masaru
authors.initials: M
authors.lastname: Ishii
authors.forename: Kenta
authors.initials: K
authors.lastname: Terai
authors.forename: Masayuki
authors.initials: M
authors.lastname: Moriya
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nakatsuji
authors.forename: Saburo
authors.initials: S
authors.lastname: Sakoda
authors.forename: Shintaro
authors.initials: S
authors.lastname: Sato
authors.forename: Shizuo
authors.initials: S
authors.lastname: Akira
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Takeda
authors.forename: Masanori
authors.initials: M
authors.lastname: Inui
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Takai
authors.forename: Masahito
authors.initials: M
authors.lastname: Ikawa
authors.forename: Masaru
authors.initials: M
authors.lastname: Okabe
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kumanogoh
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kikutani
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D001842:Bone and Bones / Q000502:physiology*; D006706:Homeostasis; D007109:Immunity; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000378:metabolism / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000172:deficiency / Q000378:metabolism / Q000502:physiology*; D011971:Receptors, Immunologic / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; C492114:Plxna1 protein, mouse; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; C498716:Trem2 protein, mouse; C484963:Tyrobp protein, mouse