Distinct requirements for TrkB and TrkC signaling in target innervation by sensory neurons
Open Access
- 1 March 2002
- journal article
- Published by Cold Spring Harbor Laboratory in Genes & Development
- Vol. 16 (5), 633-645
- https://doi.org/10.1101/gad.217902
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 (trkBshc/shc andtrkCshc/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 trkBshc/shc mice neurons lose target innervation, whereas in trkCshc/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
This publication has 44 references indexed in Scilit:
- The TrkB-Shc Site Signals Neuronal Survival and Local Axon Growth via MEK and PI3-KinaseNeuron, 2000
- NEUROTROPHINS AND SYNAPTIC PLASTICITYAnnual Review of Neuroscience, 1999
- Point Mutation in trkB Causes Loss of NT4-Dependent Neurons without Major Effects on Diverse BDNF ResponsesNeuron, 1998
- Full Activation of the Platelet-derived Growth Factor β-Receptor Kinase Involves Multiple EventsPublished by Elsevier BV ,1998
- Effects of neurotrophin and neurotrophin receptor disruption on the afferent inner ear innervationSeminars in Cell & Developmental Biology, 1997
- Signal transduction by the neutrophin receptorsCurrent Opinion in Cell Biology, 1997
- Transient expression of NMDA receptors during rearrangement of AMPA-receptor-expressing fibers in the developing inner earCell and tissue research, 1996
- Binding of Neurotrophin-3 to p75LNGFR, TrkA, and TrkB Mediated by a Single Functional Epitope Distinct from That Recognized by TrkCPublished by Elsevier BV ,1996
- Acre-transgenic mouse strain for the ubiquitous deletion ofloxP-flanked gene segments including deletion in germ cellsNucleic Acids Research, 1995
- Estimation of nuclear population from microtome sectionsThe Anatomical Record, 1946