□ DGIST’s (President Lee Kunwoo) Department of Brain Sciences Center for Synapse Diversity and Specificity (CSDS, Director Ko Jaewon) has uncovered the working principle of proteins that regulate various properties of synapses, the connection sites of nerve cells in the brain. It is expected to be used to develop treatments for brain diseases by fine-tuning the characteristics of specific synapses in neural circuits.
□ Synapses are the specialized points at which nerve cells connect with each other and are the basic units that enable all brain functions. A variety of synaptic adhesion proteins quickly and accurately transmit neural signals across these junctions, determining the nature of the neural circuit.
□ Professor Ko Jaewon and his team (CSDS) have been investigating various synaptic adhesion proteins since 2011. Especially in 2013, they showed that MDGA proteins play a role in inhibiting synaptic structure and neural signaling, and in 2017, they presented the structure and working model of this protein. However, since then, other research teams have reported conflicting results, raising questions about the exact function of MDGA proteins.
□ Using a mouse model in which genes are engineered to be deleted in specific tissues at specific times (conditional knockout), the researchers investigated the role of MDGA proteins in nerve cells. The team used confocal microscopy and electrophysiology techniques to analyze the effects of MDGA proteins on excitatory and inhibitory synapses. They found that the deletion of the MDGA1 protein increased the number and strength of inhibitory synapses, while the deletion of the MDGA2 protein increased the properties of excitatory synapses. This shows that MDGA proteins act specifically at synapses.
□ Other research teams have used genetic manipulations other than the conditional knockout model to study MDGA proteins, which has led to interpretation difficulties. However, this study ruled out extracellular MDGA protein functions and used a sophisticated gene-deletion mouse model to uncover the exact function of MDGA proteins. Specifically, the researchers found that MDGA1 and MDGA2 proteins regulate synapses in different ways. Surprisingly, deleting both proteins simultaneously abolished the changes in synaptic properties, suggesting that they are involved in the interaction between excitatory and inhibitory synapses.
□ "This is the first research that systematically analyzed the thus far controversial function of MDGA proteins in a conditional knockout mouse model," said Professor Ko. “We are currently investigating the function of the MDGA protein in cells other than neurons."
□ Dr. Kim Seungjoon (graduate of DGIST's integrated master's and doctoral program) and researcher Jang Gyubin (graduate of DGIST's master's program in Brain Sciences) at CSDS are the first authors of the study, which was published online on June 21 in the international journal Proceedings of The National Academy of Sciences of the United States of America [Impact Factor: 11.1]. The research was supported by the Ministry of Science and ICT and the Korea Research Foundation through the Leader Research Project, Mid-Career Research Project, and Sejong Science Fellowship.
- Corresponding Author E-mail Address: [email protected]
