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Sortilin associates with Trk receptors to enhance anterograde transport and neurotrophin signaling

Item Type:Article
Title:Sortilin associates with Trk receptors to enhance anterograde transport and neurotrophin signaling
Creators Name:Vaegter, C.B. and Jansen, P. and Fjorback, A.W. and Glerup, S. and Skeldal, S. and Kjolby, M. and Richner, M. and Erdmann, B. and Nyengaard, J.R. and Tessarollo, L. and Lewin, G.R. and Willnow, T.E. and Chao, M.V. and Nykjaer, A.
Abstract:Binding of target-derived neurotrophins to Trk receptors at nerve terminals is required to stimulate neuronal survival, differentiation, innervation and synaptic plasticity. The distance between the soma and nerve terminal is great, making efficient anterograde Trk transport critical for Trk synaptic translocation and signaling. The mechanism responsible for this trafficking remains poorly understood. Here we show that the sorting receptor sortilin interacts with TrkA, TrkB and TrkC and enables their anterograde axonal transport, thereby enhancing neurotrophin signaling. Cultured DRG neurons lacking sortilin showed blunted MAP kinase signaling and reduced neurite outgrowth upon stimulation with NGF. Moreover, deficiency for sortilin markedly aggravated TrkA, TrkB and TrkC phenotypes present in p75(NTR) knockouts, and resulted in increased embryonic lethality and sympathetic neuropathy in mice heterozygous for TrkA. Our findings demonstrate a role for sortilin as an anterograde trafficking receptor for Trk and a positive modulator of neurotrophin-induced neuronal survival.
Keywords:Axonal Transport, Cell Culture Techniques, Cerebral Cortex, HEK293 Cells, Hippocampus, Knockout Mice, Mammalian Embryo, Nerve Growth Factor Receptors, Neurites, Receptor Cross-Talk, Signal Transduction, Spinal Ganglia, Superior Cervical Ganglion, Vesicular Transport Adaptor Proteins, Animals, Mice
Source:Nature Neuroscience
ISSN:1097-6256
Publisher:Nature Publishing Group (U.S.A.)
Volume:14
Number:1
Page Range:54-61
Date:January 2011
Additional Information:Erratum in: Nat Neurosci 14(9):1217.
Official Publication:https://doi.org/10.1038/nn.2689
PubMed:View item in PubMed

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