Comprehensive identification of molecules at synapses and non-synaptic cell-adhesion structure

Abstract

The brain is incredibly complex and there is so much we donâ–™t know about this organ and its mechanisms. Assistant Professor Tetsuya Takano, School of Medicine, Keio University, Japan, is working to better understand neuroscience. One area of interest is neurons and astrocytes; specifically elucidating the protein component functions in each neural circuit. He and his team are working to shed light on the pathological mechanism of psychiatric and neurological disorders and, in doing so, enabling improved treatments and benefiting patients across the globe. The team has developed spatio-temporal proteome technologies: TurboID-surface and Split-TurboID, that can not only explain the formation and operation principle of neural networks, but also provide essential knowledge for research into psychiatric and neurological diseases. To overcome limitations associated with conventional proteome analysis, Takano and the team recently developed a new in vivo proximal-dependent biotin labelling (BioID) method. Using this, the researchers can label and analyse adjacent proteins with biotin, which enables them to comprehensively analyse local protein components within cells with extremely high spatial resolution. The team has used the BioID method to develop the Split-TurboID method and an innovative spatial proteome technique for searching for molecular groups among heterogeneous cells that makes it possible to comprehensively analyse the protein components in the vicinity of the adhesion site. Using the Split-TurboID method, the team has comprehensively searched for functional molecules between astrocytes and neurons and revealed that astrocytes directly control the formation of inhibitory synapses and neuronal activity in neurons via a novel tripartite synaptic molecule known as NRCAM.