Chapman Lab Paper Shows Promising New Information About Complexin Protein

Ed Chapman
Dr. Ed Chapman

A recent paper from the Chapman Lab at UW-Madison in Nature Structural and Molecular Biology just goes to show how little we still know about the way our brains work.

Ed Chapman, professor of neuroscience at the University of Wisconsin School of Medicine and Public Health, and colleagues discovered unexpected findings about a protein called Complexin – known to play a role in communication between cells in the brain. Using a reductionist approach, they discovered that complexin can form pores in bilayers and that this small soluble protein dramatically remodels membrane structure.

In other words, it can destroy cell membranes.

While setting up experiments to test a collection of different membrane-fusing proteins, a previous researcher in the Chapman lab, Huan Bao, added complexin to a simulation of cell membranes. The results were unexpected, and were not further investigated at that time.

However, other members of the Chapman lab continued to study complexin. They found that complexin is able to poke holes in simulated cells — allowing a pink dye to light up — while also bending, reordering, and ripping holes into membranes. Live videos showed the protein pinching off small bubbles of membrane while simultaneously poking holes in them.

complexin shredding cells highlighted with pink dye
Complexin is able to poke holes in simulated cells — allowing a pink dye to light up — while also ripping them into smaller bubbles. Courtesy of the Chapman lab.

Ultrahigh-resolution 3D images produced by the lab of Dorit Hanein and Niels Volkmann at the Scintillon Institute in San Diego also revealed that complexin could form twisting whorls of broken-apart membranes.

In further experiments, the team discovered some of the ways neurons might keep complexin in check. Most interestingly, the number of complexin proteins that cooperate at any one time appears to be strictly limited. In high numbers, complexin appears to ravage cells. In small, controlled quantities, it could simply promote membrane fusion.

Now that they’ve learned more about how complexin works, the team is eager to continue testing the other proteins essential in transporting neurotransmitters. Inspired by their surprising complexin discovery, they’re looking forward to carefully watching for other unexpected findings.

For full article, click below:

Courtney, K.C., Wu, L., Mandal, T. et al. The complexin C-terminal amphipathic helix stabilizes the fusion pore open state by sculpting membranes. Nat Struct Mol Biol (2022).