Postsynaptic density protein 95 (PSD-95) is transported by KIF5 to dendritic regions

• Main Authors: Ki-Seo Yoo, Kina Lee, Jun-Young Oh, Hyoeun Lee, Hyungju Park, Young Seok Park, Hyong Kyu Kim
• Format: Article
• Language: English
• Published: BMC 2019-11-01
• Series: Molecular Brain
• Subjects: PSD-95; KIF5; Glutamate receptor 1; Dendritic transport
• Online Access: http://link.springer.com/article/10.1186/s13041-019-0520-x

Abstract Postsynaptic density protein 95 (PSD-95) is a pivotal postsynaptic scaffolding protein in excitatory neurons. Although the transport and regulation of PSD-95 in synaptic regions is well understood, dendritic transport of PSD-95 before synaptic localization still remains to be clarified. To evaluate the role of KIF5, conventional kinesin, in the dendritic transport of PSD-95 protein, we expressed a transport defective form of KIF5A (ΔMD) that does not contain the N-terminal motor domain. Expression of ΔMD significantly decreased PSD-95 level in the dendrites. Consistently, KIF5 was associated with PSD-95 in in vitro and in vivo assays. This interaction was mediated by the C-terminal tail regions of KIF5A and the third PDZ domain of PSD-95. Additionally, the ADPDZ3 (the association domain of NMDA receptor and PDZ3 domain) expression significantly reduced the levels of PSD-95, glutamate receptor 1 (GluA1) in dendrites. The association between PSD-95 and KIF5A was dose-dependent on Staufen protein, suggesting that the Staufen plays a role as a regulatory role in the association. Taken together, our data suggest a new mechanism for dendritic transport of the AMPA receptor-PSD-95.