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Honing In
CHORI Scientists Provide Characterization of a Novel Lipid Binding Protein

"We have characterized a new member of a very important family of binding proteins that, it turns out, is highly expressed in primitive stem cells."

CHORI scientist Eric Soupene, PhD, and his colleagues, Vladimir Serikov, PhD, and Frans Kuypers, PhD, have just published the novel characterization of acyl-coenzyme A binding protein 6 (ACBD6) in the Journal of Lipid Research. One of a handful of major players in lipid metabolism which Dr. Kuyper’s lab has been working to elucidate, ACBD6 turns out to have potential significance for stem cell research as well. Binding proteins have the ability to bind with molecules that would be otherwise stationary and move them from one location in the body to another, not unlike UPS, points out Dr. Kuypers. Dr. Kuypers and his colleagues wanted to characterize a certain UPS truck, in this case, ACBD6, in order to better understand how and why it picks up and delivers its cargo, as well as what its cargo is.

"If you're trying to figure out what the UPS truck does, it would be very interesting to know what you can actually load into that UPS truck," says Dr. Kuypers, which was exactly where the Kuypers lab began.

In fact, what Dr. Kuypers and his colleagues determined was that ACBD6 binds only with long-chain acyl-coenzyme A (acyl-CoA), with a preference for long and unsaturated acyl chains. Characterizing this aspect of ACBD6 is only part of the picture however.

"Which proteins are expressed in which cells of the body can be particularly revealing because it may tell you something about what the protein does," says Dr. Kuypers.
"Since all the proteins in the whole body are coded in the human genome, we have the code for this binding protein, so that means we check its expression, and find out where it is in human cells."

Of 30 different human tissues Dr. Kuypers and his colleagues tested, the expression of ACBD6 appears to be limited to tissues that are rich in stem cells, primitive precursors of cells that will become specific tissues when they differentiate.

With this first-time characterization, Dr. Kuypers and his colleagues now know what kind of cargo ACBD6 carries, and in which cells of the body it carries that cargo. Now Dr. Kuypers can move on to the question of what ACBD6 does with its cargo in these particular cells.
Acyl-CoA as a molecule has many different functions in life, such as making new lipids, burning up fat, or signaling certain cell activity; this means that ACBD6 could be involved in any of those different functions.

"We think - we don't know yet - but we suspect - that ACBD6 may have a signaling role in the stem cells," says Dr. Kuypers.

This is significant, not only in terms of honing in on ACBD6 function, but also in terms of stem cell therapy.

"If you want to use stem cells for clinical application you better know what these stem cells do," explains Dr. Kuypers.

As Dr. Kuypers notes, embryonic stem cell research is still working toward a cure, while the stem cells found in cord blood, the same ones which express such high levels of ACBD6, have been used to successfully cure dozens of children already, here in CHRCO's Blood and Marrow Transplant Program, led by CHORI investigator, Mark Walter, MD.

"If you know how these stem cells proliferate without differentiating, you have a very powerful angle at improving stem cell therapy," explains Dr. Kuypers.

"If we could figure out how this binding protein maintains the stem cell in its proliferative state, rather than giving a patient 100 stem cells, you could give that same patient ten thousand stem cells."

In the mean time, the latest novel characterization provides Dr. Kuypers and his colleagues with far more clues in hand to unlock the mystery of ACBD6.

"Now we know ACBD6 binds acyl-CoA, and that it binds with a certain kind of affinity. We know that it's highly expressed in these primitive cells that are the precursors to blood cells and blood vessels."
"So then question is, what's going on? That's what's next," says Dr. Kuypers.

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Tuesday, May 17, 2011 8:19 AM

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