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Regulation of Trafficking of Activated TrkA Is Critical for NGF-Mediated Functions

  1. Author:
    Yu, T.
    Calvo, L.
    Anta, B.
    Lopez-Benito, S.
    Southon, E.
    Chao, M. V.
    Tessarollo, L.
    Arevalo, J. C.

  2. Author Address

    [Yu, Tao; Calvo, Laura; Anta, Begona; Lopez-Benito, Saray; Arevalo, Juan C.] Univ Salamanca, Dept Cell Biol & Pathol, Inst Neurociencias Castilla & Leon INCyL, Salamanca 37007, Spain. [Southon, Eileen; Tessarollo, Lino] NCI, Neurol Dev Grp, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21702 USA. [Chao, Moses V.] NYU, Sch Med, Dept Cell Biol, Mol Neurobiol Program,Skirball Inst Biomol Med, New York, NY 10016 USA. [Chao, Moses V.] NYU, Sch Med, Dept Physiol & Neurosci, Mol Neurobiol Program,Skirball Inst Biomol Med, New York, NY 10016 USA. [Chao, Moses V.] NYU, Sch Med, Dept Psychiat, Mol Neurobiol Program,Skirball Inst Biomol Med, New York, NY 10016 USA. [Chao, Moses V.] NYU, Sch Med, Dept Neurol Sci, Mol Neurobiol Program,Skirball Inst Biomol Med, New York, NY 10016 USA.;Arevalo, JC, Univ Salamanca, Dept Cell Biol & Pathol, Inst Neurociencias Castilla & Leon INCyL, Salamanca 37007, Spain.;arevalojc@usal.es
    1. Year: 2011
    2. Date: Apr
  2. Journal: Traffic
    1. 12
    2. 4
    3. Pages: 521-534
  4. Type of Article: Article
  5. ISSN: 1398-9219
  1. Abstract:

    Upon activation by nerve growth factor (NGF), TrkA is internalized, trafficked and sorted through different endosomal compartments. Proper TrkA trafficking and sorting are crucial events as alteration of these processes hinders NGF-mediated functions. However, it is not fully known which proteins are involved in the trafficking and sorting of TrkA. Here we report that Nedd4-2 regulates the trafficking of TrkA and NGF functions in sensory neurons. Depletion of Nedd4-2 disrupts the correct sorting of activated TrkA at the early and late endosome stages, resulting in an accumulation of TrkA in these compartments and, as a result of the reduced trafficking to the degradative pathway, TrkA is either reverted to the cell surface through the recycling pathway or retrogradely transported to the cell body. In addition, Nedd4-2 depletion enhances TrkA signaling and the survival of NGF-dependent dorsal root ganglion neurons, but not those of brain-derived neurotrophic factor-dependent neurons. Furthermore, neurons from a knock-in mouse expressing a TrkA mutant that does not bind Nedd4-2 protein exhibit increased NGF-mediated signaling and cell survival. Our data indicate that TrkA trafficking and sorting are regulated by Nedd4-2 protein.

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External Sources

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  2. DOI: 10.1111/j.1600-0854.2010.01156.x
  3. View record in Web of Science®
  4. WOS: 000288546900013

Library Notes

  1. Fiscal Year: FY2010-2011
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