Enzyme's alter ego helps activate the immune system

December 29, 2014

Already known to cut proteins, the enzyme SPPL3 turns out to have additional talents, according to a new study from Johns Hopkins. In its newly discovered role, SPPL3 works without cutting proteins to activate T cells, the immune system's foot soldiers. Because its structure is similar to that of presenilin enzymes, which have been implicated in Alzheimer's disease, the researchers believe their findings could shed more light on presenilin functions, in addition to providing new insight into how the immune system is controlled.

A summary of their findings was published on Dec. 22, 2014 in the journal Molecular and Cellular Biology.

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

T are that kill invading cells and help activate other . When a foreign protein binds to a receptor protein on the outside of a T cell, a signal relay system is activated. It finishes when a protein called NFAT moves to the nucleus and turns on a number of genes to fully prepare the T cell for battle. Some of what happens in between is known, but Pomerantz and his team wanted to find more players in the process.

The researchers looked for proteins that could increase NFAT's activity and found SPPL3, an enzyme that proved essential to NFAT's activation but had never before been implicated in . Further tests properly placed SPPL3 within the sequence of events that lead to NFAT activation.

SPPL3 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, which contributes to the signaling system, though it is unclear whether this is something it does directly or indirectly.

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

Pomerantz thinks that SPPL3 could be used as a drug target to either enhance the activation of T cells in immunodeficient individuals or to suppress it in those with overactive immune systems. He also plans to study the ability of SPPL3 to mediate the influx of calcium into the cell and the release of calcium from the ER, since calcium is integral to the functioning of many cell signaling networks.

Explore further: Immune system protein could explain pancreatitis

More information: Molecular and Cellular Biology, dx.doi.org/10.1128/MCB.01124-14

Related Stories

Immune system protein could explain pancreatitis

August 31, 2012
It is likely that the protein is also highly significant for other inflammatory diseases.

Self-regulation of the immune system suppresses defense against cancer

December 21, 2011
Regulatory T cells, which are part of the body's immune system, downregulate the activity of other immune cells, thus preventing the development of autoimmune diseases or allergies. Scientists at the German Cancer Research ...

Recommended for you

Study explores whole-body immunity

November 21, 2017
Over the next few months, millions of people will receive vaccinations in the hope of staving off the flu—and the fever, pain, and congestion that come with it.

Drug could cut transplant rejection

November 21, 2017
A diabetes drug currently undergoing development could be repurposed to help end transplant rejection, without the side-effects of current immunosuppressive drugs, according to new research by Queen Mary University of London ...

Atopic eczema—one size does not fit all

November 21, 2017
Researchers from the UK and Netherlands have identified five distinct subgroups of eczema, a finding that helps explain how the condition can affect people at different stages of their lives.

Breast milk found to protect against food allergy

November 20, 2017
Eating allergenic foods during pregnancy can protect your child from food allergies, especially if you breastfeed, suggests new research from Boston Children's Hospital. The study, published online today in the Journal of ...

Zika-related nerve damage caused by immune response to the virus

November 20, 2017
The immune system's response to the Zika virus, rather than the virus itself, may be responsible for nerve-related complications of infection, according to a Yale study. This insight could lead to new ways of treating patients ...

How a poorly explored immune cell may impact cancer immunity and immunotherapy

November 17, 2017
The immune cells that are trained to fight off the body's invaders can become defective. It's what allows cancer to develop. So most research has targeted these co-called effector T-cells.

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

not rated yet Dec 30, 2014
The function of this enzyme follows a recurring pattern whereby a biophysical entity may have multiple connections among different phase spaces. This is coherent with a Riemannian manifold that has a branch-point that can act upon several functional "sheaves" at once.

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.