Directing Traffic
Arnold studies how proteins navigate the neuron
By Eva Emerson
Location, location, location is usually the realtor’s mantra. But scientists studying brain cells sometimes have the same obsession.
Having a protein in the right place “is crucial for virtually everything that goes on in neurons,” says molecular neurobiologist Don Arnold, assistant professor of biology at USC College. That includes the neuron’s most basic functions—to receive, process and send impulses—which underlie humans’ ability to think, feel and move.
In turn, proteins’ correct distribution relies on a sophisticated and still poorly understood trafficking system that ferries proteins to their proper destinations within the cell.
Arnold and his team recently revealed more about the protein-transport system in neurons in a study supported by grants from the National Institutes of Health and the Whitehall Foundation. The study revealed how one family of proteins made its way to just the right place in the neuron. The researchers showed how a short section of a potassium-channel protein acted as a kind of molecular zip code—an address tag spelled in amino acids—that made sure members of the Shal family of proteins ended up in the dendrites of the neuron.
Most neurons consist of a cell center surrounded by short extensions called dendrites, which form a dense, branched mass around the cell. Connected to thousands of other neurons, dendrites receive signals. A single, long protrusion called an axon also emanates from the cell body and transmits signals, or impulses, to other neurons. Given their different functions, it makes sense that the axon and dendrite structures differ too, right down to their proteins.
“In neurons, most proteins are made in the cell body and then transported to either the dendrite or the axon or both,” says Arnold, who conducted the study with graduate student Jacqueline Rivera, former postdoctoral fellow Shoeb Ahmad, and USC College neuroscientists Emily Liman and Michael Quick.
Comparing the rat Shal protein Kv4.2 with a Shal protein from spiny lobsters, the team homed in on a stretch of just 16 amino acids that were almost identical. Arnold suspected it might be the address tag they were after.
When the team deleted the 16-amino acid tag from Kv4.2, the protein’s distribution shifted dramatically, with copies of the protein showing up throughout the neuron instead of just in the dendrite. In other tests, they added the tag to ion-channel proteins normally found in the axon. Both of the axonal proteins ended up in the dendrite. When they repeated the action with a membrane protein normally distributed throughout the cell, the result was similar.
“Our experiments show that when you can put the tag on a membrane protein, the protein will go to the dendrite, even if it normally functions elsewhere in the neuron,” Arnold says.
This basic research may one day inform studies of diseases that result from errors in protein transport. It may also help neuroscientists studying processes like learning, which are thought to involve continual changes in the structure—and thus the arrangement of proteins—of neural connections.
But to Arnold, it is the very complexity of neurons that makes them fascinating. “Neurons are unbelievably complex. A single cell can make two hundred thousand synaptic connections,” he says. “I want to find out more about the mechanisms the cell uses to create and modify these complex structures.”
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