Reverse Enzyme Helps To Activate The Immune System

The enzyme SPPL3 is already known for its protein cutting ability. Yet researchers have found that it can also work without cutting proteins to activate T cells, with structure similar to presenilin enzymes that have been implicated in Alzheimer's disease.

"No one could have predicted that SSPL3 was involved in T cell activation," said Joel Pomerantz, Ph.D., an associate professor of biological chemistry at The Johns Hopkins University, in a news release. "It walks like a duck and quacks like a duck, but its duck-like abilities don't come into play here."

T cells work as immune cells that kill invading ones and help to activate other immune cells. As a foreign protein binds to a receptor on the outside of a T cell, a signal relay system is then activated, finishing a protein known as NFAT and causing it to move to the nucleus and turn on a number of genes that fully prepare the T cell for other activity.

Researchers looked for proteins that could increase NFAT's activity and they came upon SPPL3, known as an enzyme that proved essential to NFAT's activity. Further tests properly placed SPPL3 within the sequence of events that lead to NFAT activation.

This enzyme lives in the membrane of the endoplasmic reticulum (ER), a ruffled, membrane-bound compartment inside the cell that helps process new proteins, where it seems to encourage interactions between STIM1 and Orai1, two known components of the NFAT signal relay system. But SPPL3 turned out to accomplish this without using its enzymatic, or protein-cutting, abilities. It also encourages the release of calcium from the ER that contributes to signaling. However, scientists are uncertain whether this is done directly or indirectly at this time.

"SPPL3 is a relatively uncharacterized protein that had never before been implicated in immune system function," concluded Pomerantz. "It opens up a whole new set of scientific questions."

More information regarding the findings can be seen via the journal Molecular and Cellular Biology.

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