Researchers discovered that active neurons can release an enzyme called vertebrate lonesome kinase (VLK) into the extracellular space, where it phosphorylates proteins on the outside of other cells. This extracellular phosphorylation can change how cell-surface proteins interact, and the team found that VLK boosts the function of a receptor involved in pain, learning and memory. The work was published in Science.
In experiments with mice, removing VLK from pain-sensing neurons removed the normal pain response after surgery while leaving movement and basic sensation intact. Adding extra VLK produced stronger pain responses. The investigators say the finding changes the way scientists think about neuron communication and synaptic change during learning.
The researchers note that targeting extracellular enzymes such as VLK could offer a safer strategy to modify pain pathways. This approach might avoid directly blocking NMDA receptors, which regulate nerve-cell communication but can cause serious side effects when disrupted. Controlling proteins outside the cell may also simplify drug design and reduce off-target effects because drugs would not need to enter cells.
Next steps include determining whether this mechanism applies to many proteins or only a few; if it is broader, the result could reshape treatments for neurological and other diseases. The study involved collaborators from several universities and was supported by grants from the National Institute of Neurological Disorders and Stroke, the National Institute on Drug Abuse and the National Center for Research Resources, all part of the National Institutes of Health.
- Possible advantages: safer targeting, fewer side effects, simpler drug design.
- Key question: how many proteins share this mechanism?
Difficult words
- extracellular — located or acting outside the cell membrane
- phosphorylation — addition of a phosphate group to proteins
- receptor — protein on cell surface that binds signals
- kinase — enzyme that adds phosphate groups to molecules
- synaptic — relating to connections between nerve cells
- off-target — affecting unintended molecules or biological processes
Tip: hover, focus or tap highlighted words in the article to see quick definitions while you read or listen.
Discussion questions
- If drugs targeted extracellular proteins instead of entering cells, how might patient side effects change?
- What are possible benefits and risks of reducing VLK activity to treat pain?
- How could the discovery about extracellular phosphorylation influence future treatments for neurological diseases?
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