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The Journal of Neuroscience, July 1, 2002, 22(13):5253-5258
BRIEF COMMUNICATION
Association of the Kinesin Superfamily Motor Protein KIF1B
with Postsynaptic Density-95 (PSD-95), Synapse-Associated
Protein-97, and Synaptic Scaffolding Molecule PSD-95/Discs Large/Zona
Occludens-1 Proteins
Hyejung
Mok*,
Hyewon
Shin*,
Seho
Kim,
Jae-Ran
Lee,
Jiyoung
Yoon, and
Eunjoon
Kim
Department of Biological Sciences, Korea Advanced Institute of
Science and Technology, Daejeon 305-701, Korea
Mutation in KIF1B, a kinesin superfamily motor protein,
causes a peripheral neuropathy known as Charcot-Marie-Tooth disease type 2A (CMT2A). Little is known, however, about how a defective KIF1B
gene leads to CMT2A. Here we report that KIF1B , one of the
two splice variants of KIF1B, directly interacts through its C-terminal
postsynaptic density-95 (PSD-95)/discs large/zona occludens (PDZ)
domain-binding motif with PDZ proteins including
PSD-95/synapse-associated protein-90 (SAP90), SAP97, and
synaptic scaffolding molecule (S-SCAM)-90 (SAP90). KIF1B selectively
interacts with PSD-95, SAP97, and S-SCAM in yeast two-hybrid,
pull-down, and in vivo coimmunoprecipitation experiments. KIF1B, SAP97, and S-SCAM are widely distributed to both
dendrites and axons of cultured neurons and are enriched in the small
membrane fraction of the brain. In the flotation assay, KIF1B
cofractionates and coimmunoprecipitates with PSD-95, SAP97, and S-SCAM.
These results suggest that the PSD-95 family proteins and S-SCAM have a
novel function as KIF1B receptors, linking KIF1B to its specific
cargos, and are involved in peripheral neuropathies.
Key words:
KIF1B; PSD-95; SAP97; S-SCAM; PDZ; motor; kinesin; transport; Charcot-Marie-Tooth; neuropathy
*
H.M. and H.S. contributed equally to this work.
Copyright © 2002 Society for Neuroscience 0270-6474/02/22135253-06$05.00/0
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