Key Points
- Researchers have discovered that phosphorylation—a key biochemical process—occurs outside of nerve cells, within the synapse.
- A specific kinase, VLK, is secreted by neurons and plays a crucial role in strengthening synaptic connections.
- This process is essential for learning, memory, and the sensation of pain.
- Mice lacking VLK did not develop pain hypersensitivity, suggesting that VLK could be a new target for pain-relief drugs.
Researchers have made a major discovery about how connections in our nervous system strengthen. This finding could have a big impact on our understanding of how we learn, remember, and even feel pain.
The study, published in the journal Science, focuses on a process called phosphorylation. This is when an enzyme called a kinase adds a phosphate molecule to another protein, changing its function. This process is well known to occur inside cells, but its role outside cells, especially at the tiny gaps between nerve cells called synapses, has been a mystery.
“This study gets to the core of how synaptic plasticity works—how connections between neurons evolve,” said Dr. Ted Price, one of the study’s lead authors. “It has very broad implications for neuroscience.”
The researchers found that kinases working within the synapse itself play a crucial role in strengthening these connections. “These results alter our textbook-level understanding of how synapses work,” Price said.
The team identified a specific kinase, vertebrate lonesome kinase (VLK), secreted by neurons. They discovered that after an injury, VLK is released and modifies another protein on the surface of the receiving neuron. This unique process then attracts and clusters a third type of protein, called NMDA receptors. These NMDA receptors are key players in learning and memory because they help to strengthen synaptic connections.
To test their findings, the researchers used genetically engineered mice that lacked VLK in their sensory neurons. These mice did not develop the usual post-surgical pain hypersensitivity. In contrast, when normal mice were given VLK, they showed a strong pain hypersensitivity. The team also confirmed that this mechanism also works in human tissue, highlighting the potential for new pain treatments.
Directly targeting NMDA receptors often results in serious side effects because these receptors are involved in so many aspects of the nervous system. This discovery suggests a way to indirectly control NMDA receptors by targeting VLK, potentially avoiding these side effects.
“We’re most excited about having discovered that kinases act within the synapse, not just inside neurons,” Price said. “It’s a huge update to our understanding of the basic mechanisms that regulate receptors involved in synaptic plasticity.”
