The cause of CMT Type 2A - Korean Research

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1: J Neurosci 2002 Jul 1;22(13):5253-8

Association of the Kinesin Superfamily Motor Protein KIF1Balpha with

Postsynaptic Density-95 (PSD-95), Synapse-Associated Protein-97, and

Synaptic Scaffolding

Molecule PSD-95/Discs Large/Zona Occludens-1 Proteins.

Mok H, Shin H, Kim S, Lee JR, Yoon J, Kim E.

Department of Biological Sciences, Korea Advanced Institute of Science

and

Technology, Daejeon 305-701, Korea.

ABSTRACT:

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 KIF1Balpha, 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). KIF1Balpha

selectively interacts with PSD-95, SAP97, and S-SCAM in yeast

two-hybrid, pull-down, and in vivo coimmunoprecipitation experiments.

KIF1Balpha, 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, KIF1Balpha 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 KIF1Balpha receptors, linking KIF1Balpha to its specific cargos, and

are involved in peripheral neuropathies.

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 KIF1Balpha, 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).

KIF1Balpha

selectively interacts with PSD-95, SAP97, and S-SCAM in

yeast two-hybrid,

pull-down, and in vivo coimmunoprecipitation

experiments. KIF1Balpha,

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, KIF1Balpha 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

KIF1Balpha receptors,

linking KIF1Balpha to its specific cargos, and are

involved in peripheral

neuropathies.

PMID: 12097473 [PubMed - in process]