RT Journal Article
SR Electronic
T1 JIP3 Mediates TrkB Axonal Anterograde Transport and Enhances BDNF Signaling by Directly Bridging TrkB with Kinesin-1
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 10602
OP 10614
DO 10.1523/JNEUROSCI.0436-11.2011
VO 31
IS 29
A1 Shu-Hong Huang
A1 Shan Duan
A1 Tao Sun
A1 Jue Wang
A1 Ling Zhao
A1 Zhao Geng
A1 Jing Yan
A1 Hai-Ji Sun
A1 Zhe-Yu Chen
YR 2011
UL http://www.jneurosci.org/content/31/29/10602.abstract
AB 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 NH2-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.