such as "Introduction", "Conclusion"..etc
June 25, 2009 — A protein called neuroligin
that is implicated in some forms of autism is critical to the
construction of a working synapse, locking neurons together like
"molecular Velcro," a study lead by a team of UC Davis researchers has
Published online in the June issue of the journal Neural Development,
the study is accompanied by groundbreaking images that are the first
to show two neurons coming together using neuroligin to construct a new
"Previous research has suggested that neuroligin is critical for the
formation and stabilization of synapses," said Kimberley McAllister, an
associate professor of neurology in the UC Davis School of Medicine and
a researcher at the UC Davis Center for Neuroscience. "Our work
suggests that neuroligin is one of the first molecules to be recruited
to new synapses and that it also acts as Velcro to strengthen those new
Neuroligin is a member of a family of four protein molecules that
bind to another family of proteins, the β-neurexins, across synapses.
During the past decade, scientists have observed that neuroligin is
critical for synapse formation and function, but it is only recently
that a link between the two synapse-forming molecules and autism has
been recognized, McAllister said.
Lead study author and UC Davis postdoctoral fellow Stephanie Barrow
said that researchers had hypothesized that neuroligin could facilitate
the recruitment of other proteins important in building synapses, but
no one had been able to directly visualize the process. That's because
synapses are less than 1 micron wide — 100 times narrower than a strand
of human hair. To view the process, the researchers cultured neurons
taken from newly born rats and flourescently labled the proteins —
neuroligin, PSD-95 and NMDA — which are critical to synapse formation.
"We are the first to observe that neuroligin zips around dendrites
(the branched projections of neurons) before synapses form and can
accumulate very soon after contact between cells," Barrow said.
Barrow described what the team was able to visualize: "Axons of one
neuron grow toward the dendrites of neighboring neurons. As they do so,
finger-like structures called filopodia extend and retract rapidly from
the tip of the axons and eventually make a stable contact with the
dendrite. We can then see neuroligin accumulate at these new contact
sites very rapidly, possibly stabilizing adhesion between the two
cells. After a few minutes, more neuroligin accumulates at this contact
site, bringing NMDA receptors in with it, which is then followed by a
much slower recruitment of PSD-95."
The images that accompany the study show that, indeed, the two
synaptic receptor proteins, PSD-95 and NMDA, are independently
recruited to the site of synapse formation once the connections are
locked in place by neuroligin.
"Synapses are basically specialized sites of cell adhesion that are
initially formed during development of the nervous system. Formation of
viable synapses is crucial for establishing neuronal circuits that
underlie behavior and cognition," said study senior author Philip
Washbourne, a UC Davis postdoctoral fellow when the study was initiated
and now an assistant professor of biology at the University of Oregon.
McAllister and Barrow are continuing to capture images of the
dynamics of other important molecules during synapse formation. Their
goal is to create a virtual cinematic representation that includes many
of the molecules that play important roles in the formation of a
normal, working synapse.
"Many people think that improper synapse formation leads to the
symptoms of autism," McAllister said. "This research will allow us to
learn more about how synapses form to better understand what aspects of
synapse formation might be altered in the disorder."
Other study authors include Faten El-Sabeawy of UC Davis, Eliana
Clark, formerly of UC Davis, and University of Oregon postdoctoral
fellow John Constable.
The study was funded by the Pew Charitable Trusts, the National Eye
Institute, the John Merck Fund, a UC Davis Vision Science Training
Grant, the Whitehall Foundation and Autism Speaks.
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