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Sticky blood protein yields clues to autism
Date:3/4/2008

eta3 gene as a determinant of blood serotonin levels and, independently, as a risk factor for autism, Blakely said.

In the current study, Carneiro identified a large set of proteins that stick to SERT, presuming they might control SERT activity. One of these turned out to be integrin beta3.

Once they confirmed a physical relationship between the two proteins, Blakelys team investigated whether the interaction can change SERT activity. They found that cells lacking integrin beta3 exhibit reduced serotonin uptake and that integrin beta3 activation or a human integrin beta3 mutation greatly enhances serotonin uptake.

We found that integrin beta3 can put the serotonin transporter into high gear, said Blakely. Notably, Edwin Cook, M.D., at the University of Illinois at Chicago and a co-author on the study, had shown that the same integrin beta3 mutation that elevates SERT activity also predicts elevated blood serotonin.

Most investigators studying this integrin beta3 mutation have focused on how its high activity state changes platelet clotting and never looked at its impact on serotonin levels or SERT function, explained Carneiro. Now they have a reason to.

We dont think the platelet itself contributes to autism, said Blakely, but rather we believe that the brains serotonin transporter may be controlled by integrin proteins in a very similar manner.

Carneiro and Blakely believe that too much SERT activity imposed by abnormal integrin interactions could restrict availability of serotonin in the brain during development, as well as in the adult.

What is even more striking is that this is the second time we have found elevated SERT activity associated with autism, said Blakely. In a 2005 study, Blakely and Vanderbilt collaborator James Sutcliffe, Ph.D., identified mutations in the SERT gene that triggered elevated SERT activity.

Carneiro is now hot on the trail of integrin interactions with brai
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Contact: Craig Boerner
craig.boerner@vanderbilt.edu
615-322-4747
Vanderbilt University Medical Center
Source:Eurekalert

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