JIP3 mediates TrkB axonal anterograde transport and enhances BDNF signaling by directly bridging TrkB with kinesin-1.
J Neurosci
; 31(29): 10602-14, 2011 Jul 20.
Article
em En
| MEDLINE
| ID: mdl-21775604
ABSTRACT
Brain-derived neurotrophic factor (BDNF), secreted from target tissues, binds and activates TrkB receptors, located on axonal terminals of the innervating neurons, and thereby initiates retrograde signaling. Long-range anterograde transport of TrkB in axons and dendrites requires kinesin-mediated transport. However, it remains unknown whether anterograde TrkB transport mechanisms are the same in axons versus in dendrites. Here, we show that c-Jun NH(2)-terminal kinase-interacting protein 3 (JIP3) binds directly to TrkB, via a minimal 12 aa domain in the TrkB juxtamembrane region, and links TrkB to kinesin-1. The JIP3/TrkB interaction selectively drives TrkB anterograde transport in axons but not in dendrites of rat hippocampal neurons. Moreover, we find that TrkB axonal transport mediated by JIP3 could regulate BDNF-induced Erk activation and axonal filopodia formation. Our findings demonstrate a role for JIP3-mediated TrkB anterograde axonal transport in recruiting more TrkB into distal axons and facilitating BDNF-induced retrograde signaling and synapse modulation, which provides a novel mechanism of how the TrkB anterograde transport can be coupled to BDNF signaling in distal axons.
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Base de dados:
MEDLINE
Assunto principal:
Transporte Axonal
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Transdução de Sinais
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Fator Neurotrófico Derivado do Encéfalo
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Receptor trkB
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Proteínas Adaptadoras de Transdução de Sinal
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Proteínas Associadas aos Microtúbulos
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Proteínas do Tecido Nervoso
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Neurônios
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article