PMID- 11877382 OWN - NLM STAT- MEDLINE DCOM- 20020401 LR - 20181113 IS - 0890-9369 (Print) IS - 0890-9369 (Linking) VI - 16 IP - 5 DP - 2002 Mar 1 TI - Distinct requirements for TrkB and TrkC signaling in target innervation by sensory neurons. PG - 633-45 AB - 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. FAU - Postigo, Antonio AU - Postigo A AD - European Molecular Biology Laboratory, D-69117 Heidelberg, Germany. FAU - Calella, Anna Maria AU - Calella AM FAU - Fritzsch, Bernd AU - Fritzsch B FAU - Knipper, Marlies AU - Knipper M FAU - Katz, David AU - Katz D FAU - Eilers, Andreas AU - Eilers A FAU - Schimmang, Thomas AU - Schimmang T FAU - Lewin, Gary R AU - Lewin GR FAU - Klein, Rudiger AU - Klein R FAU - Minichiello, Liliana AU - Minichiello L LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. PL - United States TA - Genes Dev JT - Genes & development JID - 8711660 RN - 0 (Adaptor Proteins, Signal Transducing) RN - 0 (Adaptor Proteins, Vesicular Transport) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Neurotrophin 3) RN - 0 (Proteins) RN - 0 (Shc Signaling Adaptor Proteins) RN - 0 (Shc1 protein, mouse) RN - 0 (Src Homology 2 Domain-Containing, Transforming Protein 1) RN - EC 2.7.10.1 (Receptor, trkB) RN - EC 2.7.10.1 (Receptor, trkC) SB - IM MH - *Adaptor Proteins, Signal Transducing MH - *Adaptor Proteins, Vesicular Transport MH - Amino Acid Motifs MH - Animals MH - Binding Sites/genetics MH - Brain-Derived Neurotrophic Factor/metabolism MH - Cochlea/innervation MH - Conserved Sequence MH - Ear, Inner/*innervation MH - Mice MH - Mice, Mutant Strains MH - Neurons, Afferent/*physiology MH - Neurotrophin 3/metabolism MH - Proteins MH - Receptor, trkB/genetics/*metabolism MH - Receptor, trkC/genetics/*metabolism MH - Shc Signaling Adaptor Proteins MH - Signal Transduction MH - Src Homology 2 Domain-Containing, Transforming Protein 1 MH - Synapses MH - Vestibule, Labyrinth/innervation PMC - PMC155354 OTO - NASA OT - NASA Discipline Developmental Biology OT - Non-NASA Center FIR - Fritzsch, B IR - Fritzsch B IRAD- Creighton U, Omaha, NE EDAT- 2002/03/06 10:00 MHDA- 2002/04/02 10:01 PMCR- 2002/09/01 CRDT- 2002/03/06 10:00 PHST- 2002/03/06 10:00 [pubmed] PHST- 2002/04/02 10:01 [medline] PHST- 2002/03/06 10:00 [entrez] PHST- 2002/09/01 00:00 [pmc-release] AID - 10.1101/gad.217902 [doi] PST - ppublish SO - Genes Dev. 2002 Mar 1;16(5):633-45. doi: 10.1101/gad.217902.