Scaffold Protein Lnx1 Stabilizes EphB Receptor Kinases for Synaptogenesis

Na Li; Si Chen; Nan-Jie Xu; Suya Sun; Jin-Jin Chen; Xian-Dong Liu

doi:10.3389/fnmol.2022.861873

Scaffold Protein Lnx1 Stabilizes EphB Receptor Kinases for Synaptogenesis

Front Mol Neurosci. 2022 Apr 21:15:861873. doi: 10.3389/fnmol.2022.861873. eCollection 2022.

Authors

Na Li^{1

2

3

4}, Si Chen^{1

2}, Nan-Jie Xu^{1

2

4

5}, Suya Sun⁶, Jin-Jin Chen^{1

2}, Xian-Dong Liu⁶

Affiliations

¹ Research Center of Translational Medicine, Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
² Department of Anatomy and Physiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
³ Shanghai Collaborative Innovation Center for Translational Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁴ Shanghai Key Laboratory of Reproductive Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁵ Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁶ Department of Neurology and Institute of Neurology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Abstract

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 Lnx1 mutant mice. Our data thus reveal a molecular mechanism whereby the Lnx1-EphB complex controls postsynaptic structure for synapse maturation during the adolescent period.

Keywords: EphB receptor; LNX1; hippocampal CA3; spine; synapse.