Two things are particularly intriguing about the team's results, reported in the June 1 issue of the journal Genes & Development.. They have been able to show, for the first time, how OPHN1 performs these roles at excitatory synapses. They have also made important progress in elucidating the pathophysiology of mutations in the OPHN1 gene.
The protein normally encoded by the OPHN1 gene belongs to what scientists call the Rho subfamily of GTP-binding proteins. "Members of this family are known to be key regulators of the actin cytoskeleton and affect many aspects of neuronal development," Van Aelst notes. The actin cytoskeleton is the gossamer, filament-like scaffolding that provides structure for the contents of cells. "All mutations that we know of in the OPHN1 gene lead to OPHN1 proteins that do not function," Van Aelst says. "This naturally raised the question of what the protein's normal function is at excitatory synapses, and what goes wrong when the gene that encodes it develops a mutation."
By manipulating OPHN1 gene expression on the postsynaptic side of the gap, the team was able to unravel a key link between OPHN1 function and synaptic activity. They showed that neuronal activity, which triggers the activation of post-synaptic cellular receptors, called NMDA receptors, is needed for the function of O
|Contact: Peter Tarr|
Cold Spring Harbor Laboratory