Sortilin associates with Trk receptors to enhance anterograde transport and signaling by neurotrophins - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Nature Neuroscience Année : 2010

Sortilin associates with Trk receptors to enhance anterograde transport and signaling by neurotrophins

Résumé

Binding of target-derived neurotrophins to Trk receptors at nerve terminals are required to stimulate neuronal survival, differentiation, innervation and synaptic plasticity. The distance between the soma and nerve terminal is tremendous, making efficient anterograde Trk transport critical for their synaptic translocation and signaling. The mechanism responsible for this trafficking remains poorly understood. Here we show that the sorting receptor sortilin interacts with TrkA, -B, and -C and enables their anterograde axonal transport, thereby enhancing neurotrophin signaling. Cultured DRG neurons lacking sortilin exhibit blunted MAPK signaling and reduced neurite outgrowth upon stimulation with NGF. Moreover, deficiency for sortilin considerably aggravates TrkA, -B- and -C phenotypes present in p75NTR knockouts, and results in increased embryonic lethality and sympathetic neuropathy in mice heterozygous for TrkA. Our findings demonstrate a novel and unexpected role for sortilin as an anterograde trafficking receptor for Trk and a positive modulator of neurotrophin-induced neuronal survival
Fichier principal
Vignette du fichier
PEER_stage2_10.1038%2Fnn.2689.pdf (124.58 Mo) Télécharger le fichier
Origine : Fichiers produits par l'(les) auteur(s)
Loading...

Dates et versions

hal-00594793 , version 1 (21-05-2011)

Identifiants

Citer

Christian Bjerggaard Vaegter, Pernille Jansen, Anja Winther Fjorback, Simon Glerup, Sune Skeldal, et al.. Sortilin associates with Trk receptors to enhance anterograde transport and signaling by neurotrophins. Nature Neuroscience, 2010, ⟨10.1038/nn.2689⟩. ⟨hal-00594793⟩

Collections

PEER
35 Consultations
96 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More