It takes a village of proteins

When a nerve cell in the brain sprouts a new “tentacle” to forge a connection with a neighbor, the proteins in the budding arm differ from those in the cell’s body, a new study shows.

Using techniques from the burgeoning field of proteomics—the effort to study the cell’s entire set of proteins—researchers tracked the concentrations of 4,855 distinct proteins in human-nerve cells. With this big-picture view of protein activity in hand, the scientists discovered how some proteins fine-tune the growth of new connections among neurons.

Understanding these key proteins might eventually lead to new therapies for Alzheimer’s disease, paralysis, and other neurological disorders, suggests team leader Richard L. Klemke of the University of California, San Diego.

“What we’re all shooting for someday is to treat some of these awful neurodegenerative diseases,” Klemke says.

The group separated nerve cell extensions called neurites from the cell bodies and then profiled the suites of proteins in the cell bodies and the neurites using a technique called large-scale mass spectrometry—a way of simultaneously identifying thousands of proteins. Of the surveyed proteins, 1,676 were more abundant in the cell bodies than in the neurites, while 1,229 were more abundant in the neurites, the team reports in the Feb. 12 Proceedings of the National Academy of Sciences.

Using databases of protein structures and functions, Klemke and his colleagues pieced together the interactions among many of these proteins. Nine proteins thought to play interchangeable roles in the formation of neurites actually control separate parts of the process, the researchers discovered.