Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Team explains how mutated X-linked mental retardation protein impairs neuron function

25.06.2014

There are new clues about malfunctions in brain cells that contribute to intellectual disability and possibly other developmental brain disorders.

Professor Linda Van Aelst of Cold Spring Harbor Laboratory (CSHL) has been scrutinizing how the normal version of a protein called OPHN1 helps enable excitatory nerve transmission in the brain, particularly at nerve-cell docking ports containing AMPA receptors (AMPARs).


False color image of a mouse hippocampal neuron (cell body is at lower right) with branchlike dendrites that provide surfaces at which projections from other neurons can connect, by forming synapses. Van Aelst and colleagues have shown that when the OPHN1 protein is mutated, interfering with its ability to interact with another protein called Homer1b/c, AMPA receptors don't recycle to the surface at synapses at the rate they normally do. This adversely impacts synaptic plasticity, the process by which neurons adjust the strength of their connections. Such pathology may play a role in X-linked mental retardation.

Credit: Van Aelst Laboratory, CSHL

Her team's new work, published June 24 in the Journal of Neuroscience, provides new mechanistic insight into how OPHN1 defects can lead to impairments in the maturation and adjustment of synaptic strength of AMPAR-expressing neurons, which are ubiquitous in the brain and respond to the excitatory neurotransmitter glutamate.

Mutations in a gene called oligophrenin-1 (OPHN1) – located on the X chromosome – have previously been linked to X-linked intellectual disability (also known as X-linked mental retardation), a condition that affects boys disproportionately and could account for as much as one-fifth of all intellectual disability among males.

Several different mutations in the OPHN1 gene have been identified to date, all of which perturb nerve cells' manufacture of OPHN1 protein. Previously, Van Aelst and colleagues demonstrated that OPHN1 has a vital role in synaptic plasticity, the process through which adjacent nerve cells adjust the strength of their connections. Cells in the brain are constantly adjusting connection strength as they respond to streams of stimuli.

The new discovery shows how OPHN1 is involved in the trafficking of AMPARs, an essential feature of plasticity in neurons. Neurons move receptors away from synapses into their interior and then back to the surface of synapses to control connection strength. At the synaptic surface, receptors provide an opportunity for the docking of neurotransmitters, in this case glutamate molecules. After a cell has fired, surface receptors are typically brought back into the interior, where they are recycled for future use.

When OPHN1 is misshapen or missing due to genetic mutation, the CSHL team demonstrated, it can no longer properly perform its role in receptor recycling, thus also impairing neurons' ability to maintain strong long-term connections with their neighbors, called long-term potentiation.

Van Aelst's new experiments explain how OPHN1 in complex with another protein called Homer1b/c should normally interact with an area called the endocytic zone (EZ) to provide a pool of AMPARs to be brought to the synapse at a location called the post-synaptic density (PSD). When OPHN1 is mutated, the pool does not form and receptors needed for strengthening synapses are not available. Long-term potentiation is impaired.

"This suggests a previously unknown way in which genetic defects in OPHN1 can lead to dysfunctions in the glutamate system," says Dr. Van Aelst. "Our earlier studies had already shown that OPHN1 is essential in stabilizing AMPA receptors at the synapse. Together, these two essential roles suggest how defective OPHN1 protein may contribute to pathology that underlies X-linked intellectual disability."

###

The research described in this release was supported by National Institutes of Health Grants RO1-MH082808 and RO1-NS082266.

"The X-linked Mental Retardation Protein OPHN1 Interacts with Homer1b/c to Control Spine Endocytic Zone Positioning and Expression of Synaptic Potentiation" appears online ahead of print in

The Journal of Neuroscience on June 25, 2014. The authors are:

Akiko Nakano-Kobayashi, Yilin Tai, Nael Nadif Kasri, and Linda Van Aelst. The paper can be obtained at: http://www.jneurosci.org

About Cold Spring Harbor Laboratory

Founded in 1890, Cold Spring Harbor Laboratory (CSHL) has shaped contemporary biomedical research and education with programs in cancer, neuroscience, plant biology and quantitative biology. CSHL is ranked number one in the world by Thomson Reuters for the impact of its research in molecular biology and genetics. The Laboratory has been home to eight Nobel Prize winners. Today, CSHL's multidisciplinary scientific community is more than 600 researchers and technicians strong and its Meetings & Courses program hosts more than 12,000 scientists from around the world each year to its Long Island campus and its China center. For more information, visit http://www.cshl.edu

Peter Tarr | Eurek Alert!

Further reports about: AMPA CSHL Harbor Neuroscience X-linked disability docking function glutamate neurons retardation synapses synaptic

More articles from Life Sciences:

nachricht Asian dust providing key nutrients for California's giant sequoias
28.03.2017 | University of California - Riverside

nachricht Chlamydia: How bacteria take over control
28.03.2017 | Julius-Maximilians-Universität Würzburg

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: A Challenging European Research Project to Develop New Tiny Microscopes

The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.

To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Researchers create artificial materials atom-by-atom

28.03.2017 | Physics and Astronomy

Researchers show p300 protein may suppress leukemia in MDS patients

28.03.2017 | Health and Medicine

Asian dust providing key nutrients for California's giant sequoias

28.03.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>