Linked Life Data

21199218

Source:http://linkedlifedata.com/resource/pubmed/id/21199218

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2011-3-25
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1600-0854
pubmed:author
pubmed:copyrightInfo
© 2011 John Wiley & Sons A/S.
pubmed:issnType
Electronic
pubmed:volume
12
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
521-34
pubmed:meshHeading
pubmed-meshheading:21199218-Animals, pubmed-meshheading:21199218-Brain-Derived Neurotrophic Factor, pubmed-meshheading:21199218-Cell Membrane, pubmed-meshheading:21199218-Cell Survival, pubmed-meshheading:21199218-Cells, Cultured, pubmed-meshheading:21199218-Endosomal Sorting Complexes Required for Transport, pubmed-meshheading:21199218-Endosomes, pubmed-meshheading:21199218-Ganglia, Spinal, pubmed-meshheading:21199218-Gene Knock-In Techniques, pubmed-meshheading:21199218-Mice, pubmed-meshheading:21199218-Nerve Growth Factor, pubmed-meshheading:21199218-Protein Transport, pubmed-meshheading:21199218-Rats, pubmed-meshheading:21199218-Receptor, trkA, pubmed-meshheading:21199218-Sensory Receptor Cells, pubmed-meshheading:21199218-Signal Transduction, pubmed-meshheading:21199218-Ubiquitin-Protein Ligases
pubmed:year
2011
pubmed:articleTitle
Regulation of trafficking of activated TrkA is critical for NGF-mediated functions.
pubmed:affiliation
Department of Cell Biology and Pathology, Instituto de Neurociencias de Castilla y León (INCyL), Universidad de Salamanca, Salamanca 37007, Spain.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Intramural