PTPσ – How A Key Protein Drives Synapse Formation

A new principle of formation of brain synapses through synaptic binding protein complexes has been identified by a research team at Daegu Gyeongbuk Institute of Science and Technology.

Many nerve cells that make up the brain control the function of the brain through synapses. Although recent studies show that synaptic binding proteins play a certain role in the formation of synapses, detailed factors or processes for collectively controlling the synapses remain unknown.

Led by Professor Jaewon Ko and Ji Won Um from Department of Brain and Cognitive Sciences, the team has been focusing on discovering related binding proteins and finding detailed mechanisms to identify the principles of formation of excitatory synapses among synapses.

PTPσ Proteins

In this study, the research team found that the interaction between the PTPσ proteins and certain bone proteins among binding proteins plays a critical role in synapse formation. In particular, they have identified that the normal tyrosine signaling mechanism resulting from the reaction of certain elements of the PTPσ proteins is an essential component of synapse formation.

Given the potential correlation between proteins and mental disorders such as autism, schizophrenia, and depression that recent large-scale human genetics studies have shown, the research team’s experiment is expected to provide important clues to help analyze the causes of brain disorders and enable treatment through further studies of related proteins.

Molecular model of PTPσ signaling pathways

Molecular model of PTPσ signaling pathways in heterologous synapse formation.
A) PTPσ triggers excitatory heterologous synapse formation through a combination of extracellular and intracellular signaling components. The PTPσ D2 domain binds intracellular adaptor proteins (e.g., liprin-α) and substrates (e.g., p250RhoGAP and N-cadherin) to recruit the vesicular machinery for excitatory synapse development.
This signal transduction model differs from that of neurexin.
B) Neurexins serve as anchor proteins that transduce postsynaptic signals from various ligands (e.g., neuroligins and leucine-rich repeat transmembrane proteins) and transfer them to adjacent, but as yet unidentified, coreceptor protein(s) to mediate the signal transduction cascades necessary for full heterologous synapse formation activity.
Credit: Daegu Gyeongbuk Institute of Science and Technology (DGIST)

Professor Ko expressed his determination by saying,

“As our recent study has reported, PTPσ proteins, along with neurexin, are considered key proteins responsible for the development of neural circuits. Our world-leading research team will conduct further studies to continue research on the development of synapses and neural circuits.”

The work was received support from the Korean Health Industry Development Institute.

Kyung Ah Han, Ji Seung Ko, Gopal Pramanik, Jin Young Kim, Katsuhiko Tabuchi, Ji Won Um, Jaewon Ko
PTPσ drives excitatory presynaptic assembly via various extracellular and intracellular mechanisms
Journal of Neuroscience 22 June 2018, 0672-18; DOI: 10.1523/JNEUROSCI.0672-18.2018

Image: Arran Lewis, Wellcome Images