What is it about?
By using brain neurons, we identified a novel molecular mechanism for neurotransmitter release regulated by two autism candidate proteins, SCAMP5 (secretory carrier membrane protein 5) and NHE6 (Na+/H+ exchanger 6). Presynaptic localization of NHE6 is mediated by direct interaction with SCAMP5. When their interaction is inhibited, proper localization of NHE6 is disrupted and the lumen of synaptic vesicle becomes hyperacidification. This leads to the reduced amount of glutamate (neurotransmitter at excitatory neuron) release from presynaptic neurons, resulting in severe defects in synaptic transmission and physiological functions of neuronal activity.
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Why is it important?
Researches about neurodevelopmental disorders at cellular level mainly dealt with the morphological changes of synaptic structures and postsynaptic functions. Recent studies suggested that several protein mutations related with the neurotransmitter release cause the neurodevelopmental disorders, however, how the protein mutations induce dysfunction in neurotransmitter release was not clearly identified. In this study, we found that autism-related proteins, SCAMP5 and NHE6, play an important role in adjusting the neurotransmitter release at presynaptic neurons. In addition, our research data provide evidences for understanding the pathological mechanism of multiple neuronal diseases because both SCAMP5 and NHE6 are considerably engaged in various neurodevelopmental, neuropsychiatric and neurodegenerative diseases.
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This page is a summary of: SCAMP5 plays a critical role in axonal trafficking and synaptic localization of NHE6 to adjust quantal size at glutamatergic synapses, Proceedings of the National Academy of Sciences, December 2020, Proceedings of the National Academy of Sciences, DOI: 10.1073/pnas.2011371118.
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