Department of Neuroscience, Genentech Inc., South San Francisco, CA, 94080, USA.
Alkahest Inc., San Carlos, CA, 94070, USA.
Sci Rep. 2020 Jul 2;10(1):10951. doi: 10.1038/s41598-020-67831-8.
The N-terminal domain (NTD) of the GluN1 subunit (GluN1-NTD) is important for NMDA receptor structure and function, but the interacting proteins of the GluN1-NTD are not well understood. Starting with an unbiased screen of ~ 1,500 transmembrane proteins using the purified GluN1-NTD protein as a bait, we identify Protocadherin 7 (PCDH7) as a potential interacting protein. PCDH7 is highly expressed in the brain and has been linked to CNS disorders, including epilepsy. Using primary neurons and brain slice cultures, we find that overexpression and knockdown of PCDH7 induce opposing morphological changes of dendritic structures. We also find that PCDH7 overexpression reduces synaptic NMDA receptor currents. These data show that PCDH7 can regulate dendritic spine morphology and synaptic function, possibly via interaction with the GluN1 subunit.
谷氨酸受体 1 亚基的 N 端结构域（GluN1-NTD）对于 NMDA 受体的结构和功能非常重要，但 GluN1-NTD 的相互作用蛋白尚未完全了解。本研究采用纯化的 GluN1-NTD 蛋白作为诱饵，通过无偏筛选约 1500 种跨膜蛋白，发现原钙黏蛋白 7（PCDH7）是一个潜在的相互作用蛋白。PCDH7 在大脑中高度表达，并与包括癫痫在内的中枢神经系统疾病有关。通过原代神经元和脑片培养，我们发现过表达和敲低 PCDH7 会诱导树突结构的相反形态变化。我们还发现 PCDH7 的过表达会减少突触 NMDA 受体电流。这些数据表明 PCDH7 可以通过与 GluN1 亚基相互作用来调节树突棘形态和突触功能。
