One area of study is the identification and characterization
of vesicular neurotransmitter transporters. These transporters mediate
the presynaptic packaging of neurotransmitters into synaptic vesicles.
The exocytotic release of neurotransmitter is dependent on vesicular
transport. Nevertheless, many of the proteins responsible for transport
and the mechanisms regulating transport remain unknown. We have recently
identified a GABA vesicular transporter in C. elegans. A vertebrate
homologue was then identified and found to be expressed in GAB Aergic
neurons in rat brain. A biochemical characterization of the vertebrate
GABA transporter revealed kinet-ics and substrate specificity similar
that for GABA transport into native synaptic vesicles isolated from
rat brain. Our results suggest that these GABA transporters are the
first identified members of a novel family of vesicular neurotransmitter
transporters.
A second area of study is the genetic basis for sensitivity and adaptation
to neuroactive com-pounds such as ethanol and other addictive drugs.
Studies in vertebrate and invertebrate systems suggest that specific
proteins mediate both the intoxicating and adaptive responses to ethanol.
As observed in other organisms, C. elegans demonstrates adaptive behavioral
responses to ethanol. We are attempting to identify the genes necessary
for the synaptic changes underlying these adaptive behavioral responses.
|
Biomedical Sciences (BMS) Graduate Program
