Association of a kinesin superfamily motor protein KIF1Bα with PSD-95, SAP97 and S-SCAM

Abstract

KIF1B is a kinesin superfamily motor protein known to transport mitochondria and synaptic vesicle precursors. KIF1B has two known splice variants, $KIF1B\alpha$ and $KIF1B\beta$. They have same N-terminal motor domain but different c-term region so their fuctions may be different in neuron. The shorter form, KIF1B, has a potential PDZ domain-binding site at its C-terminal end and the mutation of longer form, $KIF1B\beta$, is associated with the peripheral neuropathy known as Charcot-Marie-Tooth type 2A. KIF1B is abundantly expressed in brain comparing with other tissue. PSD-95, SAP97 and S-SCAM exist in presynaptic and postsynaptic sites. Their distribution is tightly organized and specialized for efficient neurotransmission. Their localization is important itself and attracts public attention because they are connected to ion channel and neurotransmitter receptor. Here we report that the C-terminus of KIF1B interacts with neuronal PDZ proteins including PSD-95/SAP90, SAP97 and S-SCAM. KIF1B interact with PSD-95, SAP97 and S-SCAM in the yeast two hybrid assay and pull down assay. KIF1B is ubiquitously distributed both in dendrites and axons of cultured neurons, which overlaps the distribution pattern of SAP97 and S-SCAM. KIF1B coimmunoprecipita -tes with PSD-95, SAP97 and S-SCAM in brain fractions. In floatation analysis, KIF1B is found in light membrane fractions along with PSD-95, SAP97 and S-SCAM, and immunoprecipitation of detergent lysates of the light membrane fractions demonstrate that KIF1B is biochemically associated with PSD-95, SAP97 and S-SCAM. These results suggest that KIF1B may be involved in the transport PSD-95 family members and S-SCAM, and perhaps their binding partners.