A new technique allows for detailed understanding of how proteins are transported in the nerve cells that connect the eye to the brain, and this may have implications for not only understanding and treating eye disease, but also for neurological diseases — including Charcot-Marie-Tooth disease (CMT).
Those findings were published in the journal Cell Reports in a paper titled, “The Retinal Ganglion Cell Transportome Identifies Proteins Transported to Axons and Presynaptic Compartments in the Visual System In Vivo.”
The proteins made in nerve cells (neurons) are critical for their ability to communicate with each other. Such communication requires proteins to move through cells, but studying this movement in detail in living organisms hasn’t really been viable— until now.
“This type of study was never possible before because it wasn’t feasible to see how these proteins move around the brain. The technology didn’t exist,” Hollis Cline, PhD, said in a press release. Cline is co-chair of the Department of Neuroscience at Scripps Research and a co-author of the new study.
Researchers used a new technique in which proteins were labeled with N-hydroxysuccinimidobiotin (NHS-biotin). That allowed them to track the movement of nearly 1,000 proteins in the neurons that connect the eyes to various parts of the brain in living rats.
“Our methodology allowed us examine the visual system in a way that had not been studied before so we could observe the molecules independently and analyze their biochemistry,” said study co-author Lucio Schiapparelli, PhD, a researcher at Scripps Research.
In rat brains — as in human brains — the retinas of the eyes is connected to various regions by neuronal axons, which are the long cell extensions that neurons use to send signals. It was in comparing proteins found in these axons to those found near/in the neurons’ nuclei (the part of the cell that stores DNA) that the researchers made a surprising discovery with relevance to CMT.
“We were surprised right from the start to find proteins in the axons of the optic nerve that everybody previously thought would be functioning only in the eye,” Cline said. “These are proteins that are usually in the nucleus of a cell, but we found them far, far away from the nucleus, participating in some form of communication.”
In other words, some of these proteins appear to be playing previously unappreciated roles in neuronal communication. And, since they can be found in neurons in other parts of the body, not just the eyes, these proteins may play a role in conditions in which neuronal communication is impaired, like CMT.
Exactly what role these proteins might be playing is still unclear and will probably require more in-depth analyses than this more “birds-eye-view” study, but the findings yield a promising starting point for further research that, according to Cline, is already underway.
And, understanding how proteins in neurons function won’t be useful just for understanding the basis of neuronal disease; it also will be crucial for developing effective treatments. “Proteins are usually the targets of drugs,” Cline explained, so to design drugs that will improve how neurons communicate with each other, “it helps to know what proteins those drugs would target.”