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Distinct requirements for TrkB and TrkC signaling in target innervation by sensory neurons

Item Type:Article
Title:Distinct requirements for TrkB and TrkC signaling in target innervation by sensory neurons
Creators Name:Postigo, A. and Calella, A.M. and Fritzsch, B. and Knipper, M. and Katz, D. and Eilers, A. and Schimmang, T. and Lewin, G.R. and Klein, R. and Minichiello, L.
Abstract: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.
Keywords:Distinct Signaling Requirements, Shc Site, Target Innervation, Trk Receptors, Animals, Mice
Source:Genes & Development
Publisher:Cold Spring Harbor Laboratory Press
Page Range:633-645
Date:1 January 2002
Official Publication:https://doi.org/10.1101/gad.217902
PubMed:View item in PubMed

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