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.

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.
Authors	Hyejung Mok, Hyewon Shin, Seho Kim, Jae-Ran Lee, Jiyoung Yoon, Eunjoon Kim
Journal	The Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci) Vol. 22 Issue 13 Pg. 5253-8 (Jul 01 2002) ISSN: 1529-2401 [Electronic] United States
PMID	12097473 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Adaptor Proteins, Signal Transducing Carrier Proteins Disks Large Homolog 4 Protein Dlg1 protein, rat Dlg4 protein, rat Intracellular Signaling Peptides and Proteins Kif1b protein, rat Magi2 protein, rat Membrane Proteins Nerve Tissue Proteins Phosphoproteins Tjp1 protein, rat Zonula Occludens-1 Protein postsynaptic density proteins Guanylate Kinases Kinesins
Topics	Adaptor Proteins, Signal Transducing Amino Acid Motifs Animals COS Cells Carrier Proteins (analysis, metabolism) Cells, Cultured Disks Large Homolog 4 Protein Guanylate Kinases Intracellular Membranes (chemistry) Intracellular Signaling Peptides and Proteins Kinesins (analysis, chemistry, metabolism) Membrane Proteins (metabolism) Nerve Tissue Proteins (analysis, chemistry, metabolism) Neurons (chemistry, metabolism) Phosphoproteins (metabolism) Precipitin Tests Rats Two-Hybrid System Techniques Yeasts (genetics) Zonula Occludens-1 Protein

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