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タイトルDistinct requirements for TrkB and TrkC signaling in target innervation by sensory neurons
著者(英)Knipper, Marlies; Katz, David; Postigo, Antonio; Minichiello, Liliana; Eilers, Andreas; Schimmang, Thomas; Calella, Anna Maria; Klein, Rudiger; Fritzsch, Bernd; Lewin, Gary R.
発行日2002-03-01
言語eng
内容記述Signaling by brain-derived neurotrophic factor (BDNF) via the TrkB receptor, or by neurotrophin-3 (NT3) through the TrkC receptor support distinct populations of sensory neurons. The intracellular signaling pathways activated by Trk (tyrosine kinase) receptors, which in vivo promote neuronal survival and target innervation, are not well understood. Using mice with TrkB or TrkC receptors lacking the docking site for Shc adaptors (trkB(shc/shc) and trkC(shc/shc) mice), we show that TrkB and TrkC promote survival of sensory neurons mainly through Shc site-independent pathways, suggesting that these receptors use similar pathways to prevent apoptosis. In contrast, the regulation of target innervation appears different: in trkB(shc/shc) mice neurons lose target innervation, whereas in trkC(shc/shc) mice the surviving TrkC-dependent neurons maintain target innervation and function. Biochemical analysis indicates that phosphorylation at the Shc site positively regulates autophosphorylation of TrkB, but not of TrkC. Our findings show that although TrkB and TrkC signals mediating survival are largely similar, TrkB and TrkC signals required for maintenance of target innervation in vivo are regulated by distinct mechanisms.
NASA分類Life Sciences (General)
権利Copyright
URIhttps://repository.exst.jaxa.jp/dspace/handle/a-is/301867


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