Firestein has worked extensively with cypin, a protein that regulates dendrite numbers (a news release is posted online at ur.rutgers.edu/medrel/viewArticle.html?ArticleID=3708). Cypin works on tubulin, a protein that is a structural building block of the dendrite skeleton. Now Firestein's research group has turned its attention to the protein snapin. When snapin binds to cypin, tubulin is crowded out, so fewer dendrites assemble and more branching occurs.
When researchers overexpressed snapin in hippocampal neurons in the lab, the number of primary dendrites growing out of the cell body decreased, but many more secondary dendrites branched off them.
"This is significant not just in identifying snapin as a protein that shapes the dendrites, but also in pinpointing a drug target where one can regulate the interaction of snapin with cypin," Firestein explained.
Both of these proteins have many other functions in the nerve cell environment and elsewhere in the body. "We need to change cypin's function for branching but not its other functions," Firestein said. "Rather than a drug that blocks cypin, we need a drug that affects the binding between the cypin and snapin. This is easier to design and cypin can still function with the other proteins it binds to."
Firestein's goal is to build "a core pathway of dendric branching" a sequence of steps, each affecting the next, with cypin at the center. "Our pathway says cypin does this; now what regulates cypin? Here snapin has a role. And what does snapin regulate?" said Firestein. "Our hope is in ten years, we will have a whole pathway mapped out so that we can target different points in the pathway with new drugs."