Soon after birth, the still-developing brain of a mammal produces too many nerve connections that create "noise" in the nervous system. The brain finds it hard to process these signals, like a person trying to have a conversation at a loud party. But as the brain matures and learning takes place, some nerve connections naturally become stronger while others weaken and die, leading to an adult with a properly wired brain.
Fragile X is caused by a mutation in a single gene, Fmr1, on the X chromosome. The gene codes for a protein called FMRP, which plays a role in learning and memory but whose full function is unknown. The protein's role in pruning nerve connections had been unclear.
"I think we've uncovered a core function for the gene involved in this disease, and if we can find other biochemical methods involved in nerve pruning, we might be able to help correct this," said Dr. Kimberly Huber, associate professor of neuroscience at UT Southwestern and senior author of the study.
In the current study, Dr. Huber and her colleagues examined nerve cells isolated from mice that had been engineered to lack the Fmr1 gene and, therefore, did not produce FMRP protein. They then tested whether the lack of FMRP affected the functions of another protein called MEF2, which is known to be involved in pruning nerve connections.
The researchers found that nerve cells lacking FMRP were unable to respond to MEF2. Adding FMRP to the cells restored MEF2's normal function.
"We were massively activating the MEF2 gene in the cell, and it did absolutely nothing without FMRP," Dr. Huber said. Such an all-or-nothing requirement in a biochemical relationship is rare, she said.
The findings also raise questions about how the two proteins interact physically. MEF2 works in the nucleus of a cell, where it controls whether other genes are turned on or off. FMRP shuttles in and out of the cell's nucleus and into its main body.
"This opens up new ideas about how processes in the cell's nucleus, near its DNA, can affect the nerve connections, which are very far away at the other end of the cell," Dr. Huber said. "We think MEF2 is making messenger RNA [ribonucleic acid], which translates the genetic code of the DNA, and FMRP is binding to the RNA and either transporting it to the nerve connections and/or controlling how the RNA makes protein."
Further research will focus on the relationship between the proteins. For instance, one might directly control the other, or they might work together on a common target, Dr. Huber said.
"This work might not have clinical implications for quite a while," she said. "The goal for us as scientists is to understand how these genes relate to mechanisms that control the development of nerve connections."
Like other genetic diseases carried on the X chromosome, Fragile X syndrome strikes boys more often and more severely than girls. Girls have two X chromosomes, so a normal gene on one chromosome can mitigate the effects of the disease if the gene on the other X chromosome is abnormal. Boys, however, have only one X chromosome, so if they inherit an abnormal gene on the X chromosome, they have no protection.
Other UT Southwestern researchers involved in the study were lead author and former graduate student Brad Pfeiffer; Dr. Tong Zang, postdoctoral researcher in neuroscience; Dr. Julia Wilkerson, postdoctoral researcher in neuroscience; Dr. Makoto Taniguchi, postdoctoral researcher in psychiatry; Marina Maksimova, research assistant in neuroscience; Dr. Laura Smith, postdoctoral researcher in psychiatry; and Dr. Christopher Cowan, assistant professor of psychiatry.
The study was funded by the National Institutes of Health, Autism Speaks, the Whitehall Foundation and Simons Foundation.
This news release is available on our World Wide Web home page at http://www.utsouthwestern.edu/home/news/index.html
To automatically receive news releases from UT Southwestern via e-mail, subscribe at www.utsouthwestern.edu/receivenews
Aline McKenzie | EurekAlert!
Newly designed molecule binds nitrogen
23.02.2018 | Julius-Maximilians-Universität Würzburg
Atomic Design by Water
23.02.2018 | Max-Planck-Institut für Eisenforschung GmbH
A newly developed laser technology has enabled physicists in the Laboratory for Attosecond Physics (jointly run by LMU Munich and the Max Planck Institute of Quantum Optics) to generate attosecond bursts of high-energy photons of unprecedented intensity. This has made it possible to observe the interaction of multiple photons in a single such pulse with electrons in the inner orbital shell of an atom.
In order to observe the ultrafast electron motion in the inner shells of atoms with short light pulses, the pulses must not only be ultrashort, but very...
A group of researchers led by Andrea Cavalleri at the Max Planck Institute for Structure and Dynamics of Matter (MPSD) in Hamburg has demonstrated a new method enabling precise measurements of the interatomic forces that hold crystalline solids together. The paper Probing the Interatomic Potential of Solids by Strong-Field Nonlinear Phononics, published online in Nature, explains how a terahertz-frequency laser pulse can drive very large deformations of the crystal.
By measuring the highly unusual atomic trajectories under extreme electromagnetic transients, the MPSD group could reconstruct how rigid the atomic bonds are...
Quantum computers may one day solve algorithmic problems which even the biggest supercomputers today can’t manage. But how do you test a quantum computer to...
For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.
In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...
Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale
Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...
15.02.2018 | Event News
13.02.2018 | Event News
12.02.2018 | Event News
23.02.2018 | Physics and Astronomy
23.02.2018 | Health and Medicine
23.02.2018 | Physics and Astronomy