Department of Medicine and Microbiology, Graduate Program in Neuroscience, College of Medicine, Chungbuk National University, 1 Chungdae-ro, Seowon-gu, Cheongju, 28644, South Korea.
Department of Structure and Function of Neural Network, Korea Brain Research Institute, 61 Cheomdan-ro, Dong-gu, Daegu, 41068, South Korea.
Mol Brain. 2019 Nov 21;12(1):97. doi: 10.1186/s13041-019-0520-x.
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.
突触后密度蛋白 95（PSD-95）是兴奋性神经元中关键的突触后支架蛋白。尽管突触区域的 PSD-95 转运和调节已经得到很好的理解，但 PSD-95 在突触定位之前在树突中的转运仍有待阐明。为了评估传统驱动蛋白 KIF5 在 PSD-95 蛋白树突转运中的作用，我们表达了一种不含 N 端运动结构域的运输缺陷型 KIF5A（ΔMD）。ΔMD 的表达显著降低了树突中的 PSD-95 水平。一致地，在体外和体内测定中，KIF5 与 PSD-95 相关联。这种相互作用是由 KIF5A 的 C 末端尾部区域和 PSD-95 的第三个 PDZ 结构域介导的。此外，ADP3（NMDA 受体和 PDZ3 结构域的关联域）的表达显著降低了树突中 PSD-95 和谷氨酸受体 1（GluA1）的水平。Staufen 蛋白对 PSD-95 与 KIF5A 的关联具有剂量依赖性，表明 Staufen 在这种关联中起调节作用。总之，我们的数据表明了 AMPA 受体-PSD-95 树突转运的一种新机制。
