JIP3 Mediates TrkB Axonal Anterograde Transport and Enhances BDNF Signaling by Directly Bridging TrkB with Kinesin-1

Abstract

Brain-derived neurotrophic factor (BDNF),

c-Jun NH2-terminal Kinase (JNK)-interacting Protein-3 (JIP3) Regulates Neuronal Axon Elongation in a Kinesin- and JNK-dependent Manner

“…4, A-C) (14). The JIP3(1-625) mutant had a similar capacity to enhance axon elongation compared with wild type JIP3 (Fig.…”

“…Four constructs were used in our studies as follows: scrambled siRNA sequence together with EGFP (scramble); fusion protein of JIP3 and EGFP (JIP3-EGFP); JIP3 siRNA sequence (14) together with EGFP (siJIP3), and JIP3 siRNA sequence together with RNAi-resistant JIP3 fused with EGFP (siJIP3 ϩ rJIP3-EGFP). The expression levels of JIP3-EGFP fusion protein were approximately twice the amount of endogenous JIP3 (Fig.…”

“…4D), suggesting that amino acids 1-625 were sufficient for JIP3 to promote axon elongation. It has been reported that several functional domains exist in the 1-625-amino acid region of JIP3, namely the kinesin binding domain (KBD) (6), JNK binding domain (JBD) (4, 6), leucine zipper-like domain (LZ) (4), coiledcoil 1 (CC1) (14), and coiled-coil 2 (CC2) (4). To more precisely define the regions required for its effect on axon elongation, four JIP3 mutants with KBD and LZ (JIP3⌬⌬), JBD (JIP3⌬JBD), and CC1 (JIP3⌬CC1) or CC2 (JIP3⌬CC2) domain deletions were constructed (Fig.…”

“…The JNK pathway is involved in axon formation/polarization, extension, synaptic plasticity, and dendrite development (7)(8)(9)(10)(11). Moreover, as a homology of UNC-16 in Caenorhabditis elegans and Sunday Driver in Drosophila, JIP3 is implicated as an adaptor protein in kinesin-dependent vesicular transport to axons (12,13) and has recently been reported to be a mediator in TrkB anterograde axonal transport in hippocampal neurons (14). Interestingly, JIP3 is selectively expressed in the embryonic and adult mouse brains (3,4).…”

JSAP1/JIP3 and JLP regulate kinesin-1-dependent axonal transport to prevent neuronal degeneration

“…21 On the other hand, JIP1 and JSAP1 were recently shown to be important for the anterograde axonal transport of plasmalemmal precursor vesicles and TrkB, respectively, in rat neurons. 22,23 Collectively, these data indicate that the regulation of axonal transport in mammals is complex, with JIPs mediating the transport of selective cargo. It is also possible that mammalian JIPs function redundantly, at least in part, in regulating axonal transport.…”