AsianScientist (Dec. 2, 2014) – A study describing the three-dimensional structure of the LAR-RPTPs/Slitrks synaptic adhesion molecule complex has been published in Nature Communications. Understanding the structure of synaptic adhesion molecules could aid in developing treatments for brain diseases such as obsessive compulsive disorder (OCD) or bipolar disorders which arise from a malfunction of synapses.
Slitrk is a protein that exists in the neuronal transmembrane and interacts with the presynaptic leukocyte common antigen-related receptor protein tyrosine phosphatases (LAR-RPTPs) to forms a protein complex. It is involved in the development of synapses in the initial stage and balances excitatory and inhibitory signals of neurons.
It is known that a disorder in those two proteins cause a malfunction of synapses, resulting in neuropsychosis such as autism, epilepsy, OCD and bipolar disorders. However, because the structure as well as synaptogenic function of these proteins were not understood, the development of treatments could not progress.
Using protein crystallography and transmission electron microscopy, a team of researchers led by Professor Kim Homin from the Korea Advanced Institute of Science and Technology (KAIST) and Professor Ko Jaewon from Yonsei University, determined the three-dimensional structure of the two synaptic adhesion molecules Slitrk and LAR-RPTPs, identifying the regions of interaction. Furthermore, they found that synapse formation is induced after the two synaptic adhesion molecules combine to develop a cluster.
“Our research findings will serve as a basis of understanding the pathogenesis of brain diseases which arises from a malfunction of synaptic adhesion molecules. In particular, this is a good example in which collaboration between structural biology and neurobiology has led to a fruitful result,” Prof. Kim said.
The article can be found at: Um et al. (2014) Structural Basis for LAR-RPTP/Slitrk Complex-Mediated Synaptic Adhesion.
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Source: KAIST.
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