15 – Three Functions of SynGAP

Event Time

December 4, 2020 at 4:00 pm


Here are our introductory comments:

Dr. Kennedy is a biochemist who studies a wide variety of proteins involved in synaptic plasticity.  She gave a great talk about specific functions of the Syngap1 protein.

Syngap1 protein is found in great abundance in the Post Synaptic Density (PSD), a subcellular structure in neurons, where signals are received from other neurons.  The PDZ domain at the far end of Syngap1 protein interacts directly with the also-abundant PSD-95 protein, localizing Syngap1 within the surface layer of the PSD.  

Phase separation is a very cool and other-worldly phenomenon.  It is the creation of a liquid-liquid interface (like oil:water not mixing), helping to organize the PSD within the neuron. Understanding phase separation will help elucidate facets of protein interactions and movements within the PSD.  

Comparing the amino acid sequences of 132 different mammalian versions of Syngap1 shows an unusually high level of sequence conservation.  One interpretation is that Syngap1 protein interacts with other proteins and itself along the entire length of the protein.

Dr. Kennedy shared her idea that Syngap1 acts as a dial to fine-tune the amount of AMPA-R at the membrane, by changing the levels of exocytosis and endocytosis.  She pointed out that this idea is different from an interpretation favored by Dr. Huganir’s lab.  When we hear that two scientists have differing interpretations we are excited, as it can lead to new experiments and important insights.  We are lucky that Syngap1 biology is being studied in multiple labs with different specialties, and we look forward to more insights from Dr. Kennedy and her lab.