Journal article
Distinct requirements for TrkB and TrkC signaling in target innervation by sensory neurons
Genes & development, Vol.16(5), pp.633-645
03/01/2002
DOI: 10.1101/gad.217902
PMCID: PMC155354
PMID: 11877382
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.
Details
- Title: Subtitle
- Distinct requirements for TrkB and TrkC signaling in target innervation by sensory neurons
- Creators
- Antonio Postigo - European Molecular Biology Laboratory, D-69117 Heidelberg, GermanyAnna Maria Calella - European Molecular Biology Laboratory, D-69117 Heidelberg, GermanyBernd Fritzsch - European Molecular Biology Laboratory, D-69117 Heidelberg, GermanyMarlies Knipper - European Molecular Biology Laboratory, D-69117 Heidelberg, GermanyDavid Katz - European Molecular Biology Laboratory, D-69117 Heidelberg, GermanyAndreas Eilers - European Molecular Biology Laboratory, D-69117 Heidelberg, GermanyThomas Schimmang - European Molecular Biology Laboratory, D-69117 Heidelberg, GermanyGary R Lewin - European Molecular Biology Laboratory, D-69117 Heidelberg, GermanyRüdiger Klein - European Molecular Biology Laboratory, D-69117 Heidelberg, GermanyLiliana Minichiello - European Molecular Biology Laboratory, D-69117 Heidelberg, Germany
- Resource Type
- Journal article
- Publication Details
- Genes & development, Vol.16(5), pp.633-645
- DOI
- 10.1101/gad.217902
- PMID
- 11877382
- PMCID
- PMC155354
- NLM abbreviation
- Genes Dev
- ISSN
- 0890-9369
- eISSN
- 1549-5477
- Publisher
- Cold Spring Harbor Laboratory Press
- Language
- English
- Date published
- 03/01/2002
- Academic Unit
- Iowa Neuroscience Institute; Biology; Craniofacial Anomalies Research Center
- Record Identifier
- 9984070867302771
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