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Protein linked to mental retardation controls synapse maturation, plasticity, CSHL team finds
Date:6/1/2009

Cold Spring Harbor, NY -- A team of neuroscientists at Cold Spring Harbor Laboratory (CSHL) has demonstrated the mechanism by which a signaling protein found throughout the brain controls the maturation and strength of excitatory synapses, the tiny gaps across which the majority of neurons communicate.

The discovery is important, in part, because deficits of the signaling protein in question, called oligophrenin-1 (OPHN1), have been previously linked with X-linked mental retardation. Indeed, problems at the synapse -- in their formation and in the mechanisms through which the strength, or plasticity, of their connections are regulated -- are thought to contribute to numerous mental and neurological disorders.

"Great progress has been made in recent years in the identification of chromosomal abnormalities and genetic changes involved in mental retardation (MR)," says Professor Linda Van Aelst, Ph.D., who led the CSHL research team. "We know of at least 280 genes that are implicated, in fact. But what we have not done, to date, is connect the genetic abnormalities associated with MR to biological processes that establish and modify the function of neuronal circuits."

That has been a major objective of studies in Van Aelst's lab, where previous experiments have shown that "knocking-down" expression of the gene that encodes the production of the OPHN1 protein (the gene is designated by the italic OPHN1) causes a potentially important change in neuronal structure. Small knob-like features, called dendritic spines, that protrude from a neuron's branch-like dendrites, typically receive signals across synapses from the axons of other neurons. Those spines were found to be abnormally short and misshapen when expression of the OPHN1 gene was acutely reduced.

A signaling protein's key functions at the synapse

In a new series of experiments, Van Aelst and colleagues set out to discover what would happen on the rec
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Contact: Peter Tarr
tarr@cshl.edu
516-367-8455
Cold Spring Harbor Laboratory
Source:Eurekalert

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