Researchers identify new route cellular proteins travel to help maintain a functioning neural network
Scientists have discovered a new pathway that ferries cellular proteins to the cell-to-cell connections, or synapses, that allow neurons to communicate with one another.
The findings, published May 4 in the Journal of Cell Biology, offer new insights into the complex ways neurons receive information and build new connections.
The levels of proteins at a cell’s surface are constantly changing in response to the cell’s environment. These proteins can be pulled back into the cell when they’re not needed, and then recycled back to the surface when they are.
“When the levels of proteins at the cell surface are altered, it alters how the cells communicate with the environment,” explains Pilar Rivero-Ríos, Ph.D., a cell biologist in the lab of Lois Weisman, Ph.D., at the University of Michigan Life Sciences Institute. “And this can lead to many types of diseases."
Two main pathways control this recycling process. The more well-known pathway works through a protein called SNX27 (short for “sorting nexin family member 27”); but a second, much less studied pathway, was recently discovered that operates through another protein called SNX17. A few studies have demonstrated that SNX17 was present in neurons, but the role of this protein in synaptic function has not been investigated.
Building on a previous study of protein recycling pathways from the Weisman lab, Rivero-Ríos wanted to determine precisely how this pathway might be at work within neurons.
Working with colleagues from the Weisman lab and the lab of Michael Sutton, Ph.D., in the Michigan Neuroscience Institute and Department of Molecular and Integrative Physiology at the U-M medical school, she studied how SNX17 moves within mammalian neurons growing in cell culture. The team found that the proteins are recruited to synaptic sites particularly during the type of cell-to-cell activity involved in a model of long-term memory formation.
When they reduced the activity of the gene that encodes the SNX17 protein, they found weaker connections and reduced plasticity between neurons, indicating that SNX17 is essential for maintaining a flexible, functioning neural network.
“The findings are relevant from a fundamental cell biology perspective, because they offer new understandings of how SNX17 acts within the cell. But also from a neuroscience perspective, we have now identified a new player involved in learning and memory formation.”
“The findings are relevant from a fundamental cell biology perspective, because they offer new understandings of how SNX17 acts within the cell,” Rivero-Ríos says. “But also from a neuroscience perspective, we have now identified a new player involved in learning and memory formation.”
“Now that we know that the SNX17 pathway is a key regulator of synapse remodeling, it will be important to determine how it is coordinated with the better understood SNX27 pathway at synaptic sites,” Sutton added.
The team next hopes to study the SNX17 pathway in the intact brain to better understand its impact on neuronal synapses.
“We already have some hints that this pathway may be involved in neurodevelopmental disorders,” says Weisman, a faculty member at the Life Sciences Institute and a professor of cell and developmental biology at the Medical School. “We want to understand those roles in the context of a more complex system, which may reveal other important functions that this protein is performing.”
Cultured neurons. The large projections form connections between neurons, which allow them to communicate signals to other neurons. Image credit: Pilar Rivero-Ríos, Weisman lab, U-M Life Sciences Institute.
Go to Article
“Recruitment of the SNX17-Retriever recycling pathway regulates synaptic function and plasticity," Journal of Cell Biology. DOI: 10.1083/jcb.202207025.