Recently, a joint research team led by Prof. Xie Wei from the School of Life Science and Technology, SEU, and the MOE Key Laboratory of Developmental Genes and 

Human Diseases,and Academician Jia Zhengping from the Center for Excellence in Brain Science and Intelligence Technology, revealed the mechanism by which the 

autism-associated molecule NLG1 regulates social memory maintenance through its cleavage products. The findings were published online in Signal Transduction and 

Targeted Therapy, an international academic journal, titled “Social memory maintenance relies on social interaction-induced proteolytic products of neuroligin 1”.

Social behavior is fundamental to animal survival and reproduction, while social memory helps animals recognize conspecifics and promotes social interaction and group 

cooperation. Deficits in social memory can impair an individual’s social behaviors, disrupt group dynamics, and thereby reduce their survival fitness. Previous research has 

indicated that the hippocampus is closely involved in the formation of social memory; however, the mechanisms underlying the maintenance of social memory remain poorly 

understood.

The research team discovered that: 1. Social interaction in animals activates ADAM10 (α-secretase) in the ventral hippocampus. This protease cleaves hundreds of 

transmembrane proteins, including synaptic cell adhesion molecules such as Neuroligins, Neurexins, and Cadherins, which can be further cleaved by γ-secretase to generate 

free intracellular domain proteins. Inhibiting the activity of ADAM10 block the formation of social memory, suggesting that ADAM10 activation and subsequent protein 

cleavage (synaptic structural remodeling) following sensory stimulation are essential for new memory formation; 2. Loss of the ADAM10 substrate NLG1 leads to impaired 

social memory maintenance, and this deficit can be rescued by supplementing with the γ-secretase cleavage product NLG1-CTD (containing the PBD domain); 3. 

Administration of the transmembrane polypeptide Tat-PBD can rescue deficits in the maintenance of various memory paradigms, including social memory, novel object 

recognition memory, and spatial memory, in the deficient mice.

This research proposes a potentially universal synaptic “Cleavage-Remodeling”model. It reveals that, following learning behavior, glutamatergic synapses in the ventral 

hippocampus undergo protease-dependent and synaptic protein-dependent structural remodeling, thereby mediating memory formation and maintenance. This provides a 

molecular basis for memory maintenance from the perspective of structural plasticity.

Associate Researcher Fellow Liu An and Ph.D. candidate Li Xingcan from the School of Life Science and Technology, SEU, are co-first authors of this paper. Prof. Xie Wei 

and Prof. Jia Zhengping are co-corresponding authors. Dr. Ren Qiaoyun, Dr. Lyu Dandan, Associate Researcher Li Moyi, and Associate Researcher Wang Yanan from the 

School of Life Science and Technology, SEU, also contributed to this study. Graduate students Zhuang Mei, Zhang Jinglei, Wu Miao, Bian Xingjie, Zhu Chengyan, and Yang 

Xiuqi are co-authors. This study was supported by the National Key R&D Program of China, major research projects of the National Natural Science Foundation of China, 

the Jiangsu Provincial Outstanding Youth Fund, and other funding sources.

Paper Link: https://doi.org/10.1126/sciadv.adz9682

Source:  School of Life Science and Technology

Translated by: Melody Zhang

Proofread by: Gao Min

Edited by: Li Xinchang