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William Green, PhD
Associate Professor
Department of Neurobiology
The University of Chicago
947 E. 58th St., MC0926
Chicago, IL 60637
Email: wgreen@midway.uchicago.edu
Phone: (773) 702-1763
Office: Abbott 412
Education
- BS Physics and Zoology (Honours),
University College,
University of Toronto
- PhD Cornell University Graduate School
of Medicine Sciences
Research Summary
Neurotransmitter receptor expression and targeting
The general focus of the research in our laboratory
is on the neurotransmitter receptors responsible for
the rapid postsynaptic response in nerve and muscle.
These receptors are members of either the molecular
family that includes nicotinic acetylcholine receptors
(AChRs), GABAA receptors, glycine receptors
or the family of ionotropic glutamate receptors. All
of these receptors are oligomeric membrane proteins
with subunits surrounding an ion channel that opens
when neurotransmitters bind to the receptor.
Subunit Folding and Assembly of the "Muscle-Type" Nicotinic
AChR
One of our projects is to understand how nerve and
muscle cells fold and assemble the subunits into a
functioning receptor and express it in the postsynaptic
membrane. The AChR was chosen because its composition
and stoichiometry is known. The AChR is composed of
four subunits, a, b, g and d, that assemble into a2bgd
pentamers. In order to make precise measurements of
the AChR subunits in vivo, the AChR subunit cDNAs cloned
from the ray Torpedo californica and from mouse have
been stably integrated into the genome of mammalian
tissue culture cell lines. Expression of the AChRs
in these foreign cells allows large amounts of the
receptors to be grown up for biochemical and functional
assays and allows the AChRs to be studied in the absence
of other synaptic proteins, which might otherwise complicate
our studies. Using a variety of recombinant DNA, biochemical
and pharmacological techniques, we are presently dissecting
the events involved in the AChR subunit folding and
assembly.
Neuronal Nicotinic AChRs
Nicotinic AChR receptors are found in the central
and peripheral nervous systems of almost all animals.
As the site where nicotine binds in the brain, these
receptors are responsible for nicotine addiction and
may also play a role in Alzheimer's disease. Neuronal
AChRs differ from the muscle-type AChRs in that they
are subdivided into distinct pharmacological subtypes.
Each subtype appears to be composed of a different
set of subunit isoforms. These subunits are distinct
from, yet homologous to the muscle subunits. We are
searching for the subunit composition of these neuronal
AChR subtypes. Different combinations of the subunit
cDNAs will be expressed in mammalian cell lines system
to see if specific pharmacological properties of a
subtype can be reproduced in this reconstituted system.
Attempts will also be made to identify subunit composition
by purifying the receptor subtypes from different neuronal
sources.
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