USC (US) — Using bioluminescent proteins from a jellyfish, scientists have lit up the inside of a neuron and captured footage of proteins moving throughout the cell.
The video offers a rare peek at how proteins, the brain’s building blocks, are directed through neurons to renew its structure.
“Your brain is being disassembled and reassembled every day,” says Don Arnold, associate professor of molecular and computational biology at University of Southern California (USC), and corresponding author of an article about the research published in Cell Reports.
“One week from today, your brain will be made up of completely different proteins than it is today,” Arnold says. “This video shows the process. We’ve known that it was happening, but now we can watch it happen.”
The new imaging technique was used to cast new light on how proteins are directed to one of the two types of compartments inside the neuron: the axon or the dendrites.
The axon is the region of the cell responsible for transmitting electrical signals to other cells, while the dendrites receive signals from other cells.
“It’s been known for many decades that proteins are specifically targeted to one compartment or the other. However, we couldn’t understand how the targeting occurs until we could actually watch the proteins traveling to one compartment or to the other,” says Sarmad Al-Bassam, a Ph.D. student at USC and lead author of the article.
Since the mid-1990s, scientists have been able to illuminate the proteins inside of cells, including neurons, by attaching a protein isolated from jellyfish—known as GFP (green fluorescent protein)—that fluoresces bright green when exposed to blue light.
Martin Chalfie of Columbia University, Roger Tsien of the University of California-San Diego, and Osamu Shimomura of Boston University were awarded the Nobel Prize in Chemistry in 2008 for the discovery and development of GFP.
The problem with studying the flow of illuminated proteins inside of neurons is that there are several different overlapping pathways within the cell, making it difficult to study the traffic through just one.
Al-Bassam and his colleagues solved this issue by developing a new technique that involves damming up a single pathway, which creates a backlog of transport vesicles—little bubbles that travel up and down neurons carrying membrane protein cargo—impregnated with the illuminated proteins. They then use a small-molecule drug to release the backlog all at once in a bright pulse.
“Our result was very surprising,” says Arnold. “We found that rather than being targeted specifically to the dendrites, vesicles carrying proteins initially enter both compartments, but then are stopped and prevented from moving beyond the initial segment of the axon.”
Al-Bassam and Arnold worked with USC postdoctoral fellow Min Xu as well as Thomas J. Wandless, professor at Stanford University.
This research was funded by the National Institutes of Health.