2016年度秋季学期学术系列讲座之十
题目：The "Serine Shuttle": A glia-neuron crosstalk important for synaptic plasticity and learning and memory
讲座人：Herman Wolosker, M.D., Ph.D.
Professor
Department of Biochemistry
Technion-Israel Institute of Technology
The B. Rappaport Faculty of Medicine
Israel
时间：2016年11月11日，13:00 - 14:30
地点：威廉希尔邓祐才报告厅
联系人：饶毅
摘要：
Our laboratory has been studying the neurobiology of D-serine, a D-amino acid which is increasingly appreciated as an important transmitter/signaling molecule. D-Serine modulates N-methyl D-aspartate receptors (NMDARs) and regulates synaptic plasticity, neurodevelopment, and learning and memory. However, the primary site of D-serine synthesis and release remains controversial, with some arguing that it is a gliotransmitter and others defining it as a neuronal cotransmitter. We found that the biosynthetic enzyme of D-serine, serine racemase (SRR), is expressed almost entirely by neurons, with few astrocytes appearing to contain D-serine. Instead of producing D-serine, we found that astrocytes mainly export L-serine to neurons to fuel the synthesis of D-serine by the neuronal SRR. This metabolic cross-talk, called "serine shuttle", appears to be the main determinant of D-serine, and possibly glycine levels as well. Genetic studies and knockout mice models now implicate six serine shuttle genes (PHGDH, PSAT1, SLC1A4, SLC7A10, SRR and DAO) in severe neurological problems, mental disability, and in neuropsychatric disease as well. In the seminar, we will present an overview of the serine shuttle mechanisms and present recent data on the roles of some of its components in NMDAR synaptic plasticity, learning and memory, and motoneuron function.
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