Science, Space and Technology News 2024
Researchers at Johns Hopkins Medicine have uncovered a new role of the SYNGAP1 gene in memory and learning, showing its significance beyond enzyme activity to include scaffolding functions at synapses. This finding, which reveals the gene’s dual role in regulating synaptic strength and plasticity, could lead to better treatments for children with neurodevelopmental disorders linked to SYNGAP1 mutations.
But, working with the SynGAP protein, Huganir and others had begun to see that SynGAP proteins have a strange property when they interact with the major synaptic scaffolding protein, PSD-95. They morph into liquid droplets.Neuron showing SynGAP binding to PSD-95 at synapses. Credit: Yoichi Araki and Rick Huganir, Johns Hopkins Medicine
The research team next did the same type of genetic engineering in mice to remove the enzymatic function of SynGAP, and found similar results: Synapses behaved normally, with no problems in synaptic plasticity, and the mice had no difficulty in learning and memory behaviors. The research team says this indicates that SynGAP’s structural property was sufficient for normal cognitive behavior.
“This sequence happens without the catalytic activity typical of SynGAP,” says Huganir. Rather, SynGAP corrals PSD-95 when bound to it, but when SynGAP leaves this synapse, PSD-95 is open to bind to AMPA receptor/TARP complexes.
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