Li Na, Chen Si, Xu Nan-Jie, Sun Suya, Chen Jin-Jin, Liu Xian-Dong
Research Center of Translational Medicine, Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Anatomy and Physiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Front Mol Neurosci. 2022 Apr 21;15:861873. doi: 10.3389/fnmol.2022.861873. eCollection 2022.
Postsynaptic structure assembly and remodeling are crucial for functional synapse formation during the establishment of neural circuits. However, how the specific scaffold proteins regulate this process during the development of the postnatal period is poorly understood. In this study, we find that the deficiency of ligand of Numb protein X 1 (Lnx1) leads to abnormal development of dendritic spines to impair functional synaptic formation. We further demonstrate that loss of Lnx1 promotes the internalization of EphB receptors from the cell surface. Constitutively active EphB2 intracellular signaling rescues synaptogenesis in mutant mice. Our data thus reveal a molecular mechanism whereby the Lnx1-EphB complex controls postsynaptic structure for synapse maturation during the adolescent period.
突触后结构组装和重塑对于神经回路建立过程中功能性突触的形成至关重要。然而，在出生后发育阶段，特定支架蛋白如何调节这一过程却知之甚少。在本研究中，我们发现麻木蛋白X1配体（Lnx1）的缺失会导致树突棘发育异常，从而损害功能性突触的形成。我们进一步证明，Lnx1的缺失会促进EphB受体从细胞表面内化。组成型激活的EphB2细胞内信号传导可挽救突变小鼠的突触发生。因此，我们的数据揭示了一种分子机制，即Lnx1-EphB复合物在青春期控制突触后结构以实现突触成熟。
