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

  1. Author:
    Vaegter, C. B.
    Jansen, P.
    Fjorback, A. W.
    Glerup, S.
    Skeldal, S.
    Kjolby, M.
    Richner, M.
    Erdmann, B.
    Nyengaard, J. R.
    Tessarollo, L.
    Lewin, G. R.
    Willnow, T. E.
    Chao, M. V.
    Nykjaer, A.

  2. Author Address

    [Vaegter, Christian B.; Jansen, Pernille; Glerup, Simon; Skeldal, Sune; Kjolby, Mads; Richner, Mette; Nykjaer, Anders] Aarhus Univ, Dept Med Biochem, Lundbeck Fdn, Res Ctr MIND, Aarhus, Denmark. [Fjorback, Anja W.; Nyengaard, Jens R.] Aarhus Univ, Stereol & Electron Microscopy Lab, Lundbeck Fdn, Res Ctr MIND, Aarhus, Denmark. [Erdmann, Bettina; Lewin, Gary R.; Willnow, Thomas E.] Max Delbruck Ctr Mol Med, Berlin, Germany. [Tessarollo, Lino] NCI, Ctr Canc Res, Frederick, MD 21701 USA. [Chao, Moses V.] NYU, Sch Med, Skirball Inst Biomol Med, Kimmel Ctr, New York, NY USA.;Nykjaer, A, Aarhus Univ, Dept Med Biochem, Lundbeck Fdn, Res Ctr MIND, Aarhus, Denmark.;cv@biokemi.au.dk an@biokemi.au.dk
    1. Year: 2011
    2. Date: Jan
  2. Journal: Nature Neuroscience
    1. 14
    2. 1
    3. Pages: 54-U78
  4. Type of Article: Article
  5. ISSN: 1097-6256
  1. 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.

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External Sources

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  2. DOI: 10.1038/nn.2689
  3. View record in Web of Science®
  4. WOS: 000285684900014

Library Notes

  1. Fiscal Year: FY2010-2011
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