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BIOGRAPHY:
Dr. Labarca is Professor of Biophysics at the Center for Scientific Studies in Valdivia, Chile. After receiving a Ph.D. from the Biophysics Program at Brandeis University, Waltham, Massachusetts, he conducted postdoctoral research in biophysics at the University of California-San Diego and then returned to Chile as a Visiting Professor, Faculty of Biological Sciences, at the Catholic University of Chile in Santiago. He received a postdoctoral fellowship from the Muscular Dystrophy Association (1981-1982) and a Guggenheim Fellowship in 1995. Dr. Labarca was awarded the 1994-1995 Catedra Patrimonial de Excelencia from CONACYT, Mexico, and was elected President of the Latin American Society of Biophysicists in 1995. In 1996 he was named a Chilean Presidential Chair in Science and, in 1999, was awarded the Rector's Medal from the University of Chile. He first received an HHMI International Research Scholar award in 1997. His current HHMI-funded project is entitled "Altered Synaptic Vesicle Function in ipp, a Drosophila Mutant of Inositol Metabolism, is Mimicked by Lithium and Rescued by Exogenous Inositol."
RESEARCH ABSTRACT SUMMARY:
Altered Synaptic Vesicle Function in ipp, a Drosophila Mutant of Inositol Metabolism, is Mimicked by Lithium and Rescued by Exogenous Inositol
In addition to their roles in intracellular signaling,
phosphoinositides (PI) are important regulators of membrane traffic at
the synapse. We used FM1-43 imaging to investigate synaptic vesicle
(SV) function at presynaptic terminals of ipp, a
Drosophila mutant of the lithium-sensitive enzyme inositol
polyphosphate 1-phosphatase. This enzyme participates in the recovery
of inositol, is needed for PI synthesis from inositol polyphosphates,
and is a putative target of lithium in managing bipolar disorder. The
mutation in ipp, as well as lithium, would be expected to
deplete inositol, thus depressing Pi-dependent mechanisms. Previously,
ipp synapses were reported to exhibit abnormal neurotransmitter
release properties, which were mimicked by lithium in normal synapses.
We found that synaptic vesicle trafficking is grossly impaired in
ipp, and this deficiency was mimicked by lithium in normal
synapses. Exogenous inositol restored to normal SV trafficking as well
as synaptic transmission in ipp and prevented the effects of
lithium in normal individuals. Our results provide the first evidence
that inositol depletion can alter SV trafficking and neurotransmitter
release at the synapse and point to Pi-dependent regulation of SV
function at nerve endings as a target of mood stabilizers.
Photo: Kent Kallberg Studios
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