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Publication : Indispensable role of Nectin-like 4 in regulating synapse-related molecules, synaptic structure, and individual behavior.

First Author  Liu X Year  2023
Journal  FASEB J Volume  37
Issue  6 Pages  e22970
PubMed ID  37184041 Mgi Jnum  J:341975
Mgi Id  MGI:7541653 Doi  10.1096/fj.202101468RRRR
Citation  Liu X, et al. (2023) Indispensable role of Nectin-like 4 in regulating synapse-related molecules, synaptic structure, and individual behavior. FASEB J 37(6):e22970
abstractText  Nectin-like family members (Necls) are involved in synaptic organization. In contrast to that of Necl-2/CADM1/SynCAM1, which is critical in synaptic events, investigation of Necl-4/CADM4/SynCAM4 in synapses has largely lagged behind given the particularity of homophilic self-interactions compared to interactions with other Necls. We sought to further understand the role of Necl-4 in synapses and found that knockout of Necl-4 led to aberrant expression levels of proteins mediating synaptic function in cortex homogenates and augmented accumulation of ionotropic glutamate receptor in postsynaptic density fractions, although a compensatory effect of Necl-1 on the expression levels existed. Concurrently, we also found increased synaptic clefts in the cortex and simplified dendritic morphology of primary cultured cortical neurons. Experiments on individual behaviors suggested that compared to their wild-type littermates, Necl-4-KO mice exhibited impaired acquisition of spatial memory and working memory and enhanced behavioral despair and anxiety-like behavior. These findings suggest that Necl-4 mediates synaptic function and related behaviors through an indispensable role and offer a new perspective about collaboration and specialization among Necls.
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