The empirical dependency adjustment of the brain circuit depends on the dynamic changes of synaptic connections guided by neuronal activity, in particular post-synaptic maturation requiring morphological changes in dendritic spines, targeting postsynaptic proteins and insertion of synaptic neurotransmitter receptors. Therefore, it is important to understand how neuronal activity controls post-synaptic maturation.
Prof. Nancy Y. Ip from HKUST has led her team to conduct an in-depth study of the problem. The results were published in the prestigious scientific journal, Proceedings of the National Academy of Sciences (PNAS, influencing factor 9.803). Professor Nancy Y. Ip studied and reported that the scaffold protein liprinα1 and its phosphorylation regulate the synaptic distribution of postsynaptic protein 95 (PSD-95) and thus have a significant effect on the maturation of excitatory synapses. Cyclin-dependent kinase Cdk5 phosphorylates the threonine 701 site of liprinα1, and this phosphorylation is regulated by neuronal activity. When the neuronal activity increases, the phosphorylation of this site is reduced. Blocking the phosphorylation of liprinα1 promotes the structural and functional maturation of excitatory synapses. The team cleverly applied the super-resolution imaging technology from NBI to reveal how the co-localization of liprinα1 and PSD-95 at the nanoscale is affected by the phosphorylation of liprinα1. They performed dual-channel super-resolution imaging of the two proteins, demonstrating that when liprinα1 phosphorylation was inhibited, the co-localization of both favored the rise, providing intuitive evidence of the interaction between the two proteins.
Prof. Nancy Ip is a member of the International Society of Molecular Neuroscience, also a member of the Chinese Academy of Sciences, foreign academician of the US National Academy of Sciences, academician of the World Academy of Sciences, and academician of the Hong Kong Academy of Sciences. Prof. Nancy Ip and co-author Professor Du Shengwang are the founders of the super-resolution imaging center of the Hong Kong University of Science and Technology. Professor Du Shengwang is also one of the founders of NBI. The paper's experiments are supported by a prototype of NBI SRiS 2.0, one NBI dual-channel super-resolution microscope.
Fig. 3, Phosphorylation of liprinα1 regulates the synaptic distribution of PSD-95. The super-resolution microscope is used to reconstruct the cell imaging of synaptophysins and to provide extremely accurate information on protein interactions and protein distribution. Ros treatment (Ros group, right in Figure C) inhibited the phosphorylation of liprinα1, and the co-localization of liprinα1 and PSD-95 was significantly higher than that of the control group (Con group).
Fig. 4, When the phosphorylation of liprinα1 was inhibited by small interfering peptides, the co-localization of liprinα1 and PSD-95 increased. STORM images provide evidence for quantitative analysis of both distribution and co-localization. Small interfering polypeptide-treated neurons (siLIP group, right in Figure C) increased co-localization of liprinα1 and PSD-95 relative to randomized peptide-treated controls (see the table, see left).