I had tried to replicate this one because it looked so good!

Dissociation of SYNGAP1 enzymatic and structural roles: Intrinsic excitability and seizure susceptibility | PNAS SYNGAP1 is a key Ras-GAP protein enriched at excitatory synapses, with mutations causing intellectual disability and epilepsy in humans. Recent stu...

Now published in PNAS! Congrats to my amazing colleagues Julia and Blaise & postdoctoral mentor Rick! www.pnas.org/doi/10.1073/...

Here we've dissociated enzymatic vs structural roles of SYNGAP1 in neuronal physiology and seizure susceptibility. This will inform treatment development for this NDD!

Congrats to my dear colleagues Julia Brill, Blaise Clarke, and @rhuganir.bsky.social! And thanks to the many people who helped with this research. Lastly, thanks to
@curesyngap1.bsky.social and all Syngapian families who inspired our science.

Seizures and epilepsy are serious symptoms of #SYNGAP1 syndrome, which arises from LoF mutations in the gene. Our finding has important implications in the treatment of this condition because it shows that the structural role of SYNGAP1 will need to be rescued by therapies.

This unexpected structural role was discovered when
#YoichiAraki made GAP-deficient* mutant Syngap1 mice & explored LLPS with other molecules. GAP-regulation of intrinsic excitability builds on earlier findings by #GavinRumbaugh & establishes SYNGAP1 as a bifunctional molecule.

Excited to share our new preprint on #SYNGAP1 that shows how its enzymatic and structural role can be dissociated! The GAP activity is essential in increasing intrinsic excitability but does not contribute to the seizure protection SynGAP is important for: biorxiv.org/content/10.1...

Preprint of our new manuscript describing the differential enzymatic and structural roles of SYNGAP1. These findings highlight the complex interplay between SYNGAP1 structural and catalytic functions in neuronal physiology and disease.
www.biorxiv.org/content/10.1...