School of Medicine, Zhejiang University City College, Hangzhou, Zhejiang, People's Republic of China.
College of Clinical Medicine, NingXia Medical University, Yinchuan, Ningxia, People's Republic of China.
Neurosci Lett. 2019 Aug 10;707:134291. doi: 10.1016/j.neulet.2019.134291. Epub 2019 May 23.
Protein Numb localizes to clathrin-coated vesicles and participates in the trafficking of trans-membrane receptors. We previously reported that Numb deficiency in cerebellar Purkinje cells impairs synaptic expression of metabotropic glutamate receptor 1 (mGlu1) and motor coordination. However, the functions of Numb in other brain regions have not been investigated. Here, we show that Numb regulates the membrane expression of metabotropic glutamate receptor 5 (mGlu5) and is critical to social behaviors. Numb binds to mGlu5 and promotes the membrane expression of mGlu5 by antagonizing its internalization and recycling. Interestingly, the conditional knockout of Numb and its homologous gene, Numblike, in excitatory neurons leads to a significant deficit in the three-chamber social test. Together, our work suggests that Numb is required for social interaction by modulating the functions of mGlu5.
蛋白 Numb 定位于网格蛋白包被小泡，参与跨膜受体的运输。我们之前的研究表明，小脑浦肯野细胞中 Numb 的缺失会损害代谢型谷氨酸受体 1（mGlu1）的突触表达和运动协调。然而，Numb 在其他脑区的功能尚未被研究。在这里，我们发现 Numb 调节代谢型谷氨酸受体 5（mGlu5）的膜表达，对社会行为至关重要。Numb 与 mGlu5 结合，并通过拮抗其内化和再循环来促进 mGlu5 的膜表达。有趣的是，兴奋性神经元中 Numb 和其同源基因 Numblike 的条件性敲除导致三箱社交测试中存在显著缺陷。总之，我们的工作表明，Numb 通过调节 mGlu5 的功能来参与社交互动。
