Type 2A Mutation Research from Korea

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(Very technical abstract, however, those with Type 2A might be

interested)

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.