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The Journal of Neuroscience, January 1, 2003, 23(1):131-140
KIF17 Dynamics and Regulation of NR2B Trafficking in Hippocampal
Neurons
Laurent
Guillaud,
Mitsutoshi
Setou, and
Nobutaka
Hirokawa
Department of Cell Biology and Anatomy, Graduate School of
Medicine, University of Tokyo, Bunkyo-ku Tokyo 113-0033, Japan
KIF17, a recently characterized member of the kinesin superfamily
proteins, has been proposed to bind in vitro to a
protein complex containing mLin10 (Mint1/X11) and the NR2B subunit of the NMDA receptors (NMDARs). In the mammalian brain, NMDARs play an
important role in synaptic plasticity, learning, and memory. Here we
present, for the first time, the dynamic properties of KIF17 and
provide evidence of its function in the transport of NR2B in living
mammalian neurons. KIF17 vesicles enter and move specifically along
dendrites in a processive way, at an average speed of 0.76 µm/sec. These vesicles are effectively associated with
extrasynaptic NR2B, and thus they transport and deliver NR2B subunits
in dendrites. However, KIF17 does not seem to enter directly into
postsynaptic regions. Cellular knockdown or functional blockade of
KIF17 significantly impairs NR2B expression and its synaptic localization. Interestingly, the decrease in the number of synaptic NR2B subunits is followed by a parallel increase in the number of NR2A
subunits at synapses. In contrast, upregulation of the expression level
of NR2B, after treatment with the NMDAR antagonist D( )-2-amino-5-phosphonopentanoic acid,
simultaneously increases the expression level of KIF17. These
observations concerning the downregulation or upregulation of KIF17 and
NR2B reveal the probable existence of a shared regulation process
between the motor and its cargo. Taken together, these results
illustrate the complex mechanisms underlying the active transport and
regulation of NR2B by the molecular motor KIF17 in living hippocampal neurons.
Key words:
KIF17; kinesin; NR2B; NMDA receptor; hippocampal
neuron; mLin10; YFP; dynamics; regulation; antisense oligonucleotides; dominant negative; AP-V
Copyright © 2003 Society for Neuroscience 0270-6474/03/231131-10$05.00/0
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