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.
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.
Mok
Hyejung
H
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea.
Shin
Hyewon
H
Kim
Seho
S
Lee
Jae-Ran
JR
Yoon
Jiyoung
J
Kim
Eunjoon
E
D048868:Adaptor Proteins, Signal Transducing; D020816:Amino Acid Motifs; D000818:Animals; D019556:COS Cells; D002352:Carrier Proteins / Q000032:analysis / Q000378:metabolism*; D002478:Cells, Cultured; D000076122:Disks Large Homolog 4 Protein; D051528:Guanylate Kinases; D007425:Intracellular Membranes / Q000737:chemistry; D047908:Intracellular Signaling Peptides and Proteins; D016547:Kinesins / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D009474:Neurons / Q000737:chemistry / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism; D011233:Precipitin Tests; D051381:Rats; D020798:Two-Hybrid System Techniques; D015003:Yeasts / Q000235:genetics; D062826:Zonula Occludens-1 Protein
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D000076122:Disks Large Homolog 4 Protein; C501119:Dlg1 protein, rat; C501449:Dlg4 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; C490399:Kif1b protein, rat; C114103:Magi2 protein, rat; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; C569044:Tjp1 protein, rat; D062826:Zonula Occludens-1 Protein; C033652:postsynaptic density proteins; D051528:Guanylate Kinases; D016547:Kinesins