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The
goal of the Hurley group is to develop a molecular understanding of
light and dark adaptation in the vertebrate retina. When a retina is
dark-adapted an increase in illumination of only a few photons per
second can be detected and reported to the brain. When a retina is
light adapted it can report changes in illumination on a backgrounds of
billions of photons per second. How can a tissue respond with such
extreme sensitivity under one condition and avoid saturation under
intense stimulation under other conditions? Within the retina there are
two types of photoreceptors, rods and cones. Rods are specialized for
extraordinary sensitivity; they can detect single photons Cones are
specialized for adaptation. Responses of cones do not saturate even
under conditions of extremely intense illumination.
Previously
Dr. Hurley and his colleagues focused their efforts on identifying and
characterizing proteins in rods and cones that are required for
transduction of light into an electrical change in rods and cones.
These proteins include rhodopsin, transducin, cGMP phosphodiesterase
and guanylyl cyclase. More recently, the group has focused on other
enzymes that modulate the phototransduction mechanism, including GCAPs,
recoverin and rhodopsin kinase. Measurements of biochemical activities
and understanding of regulatory mechanisms have been the focus of those
studies.
Most
recently, the focus of the group has broadened to pursue an
understanding of how the biochemical activities of these enzymes
actually contribute to vision. Animals, both mice and zebrafish, with
genetic alterations that affect the activities of specific proteins
involved in rod or cone function are being analyzed. Sophisticated
biochemical, electrophysiological and behavioral strategies are being
used to directly evaluate the contributions of these proteins to the
viability of photoreceptors and to vision over a wide range of
illumination conditions.
Selected
Publications
Brockerhoff,
S.E., Rieke, F., Matthews, H.R., Taylor, M.R., Kennedy, B.,
Ankoudinova, I., Niemi, G.A., Tucker, C.L., Xiao, M., Cillufo, M.C.,
Fain, G.L. and Hurley, J.B. (2003). Light stimulates a
transducin-indepdendent increase of cytoplasmic Ca 2+ and suppression
of current in cones from the zebrafish mutant nof. J. Neurosci. 23
:47-480.
Kennedy,
M.J., Sowa, M.E., Wensel, T.G. and Hurley, J.B. (2003). Acceleration of
key reactions as a strategy to elucidate the rate-limiting chemistry
underlying phototransduction inactivation. Invest. Ophthalmol. Vis. Sci
. 44 : 1016-22.
Ramamurthy
V,, Roberts M., van den Akker F., Niemi G., Reh T.A., Hurley J.B.
(2003). AIPL1, a protein implicated in Leber's congenital amaurosis,
interacts with and aids in processing of farnesylated proteins. Proc.
Natl. Acad. Sci. USA. 100:12630-5.
Taylor
, M.R., Hurley, J.B. Van Epps, H.A. and Brockerhoff, S.E. (2004). A
zebrafish model for pyruvate dehydrogenase deficiency: rescue of
neurological dysfunction and embryonic lethality using a ketogenic
diet. Proc. Natl. Acad. Sci. USA 101:4584-9.
Kennedy,
M.J. , Dunn, F.A. and Hurley, J.B. (2004). Visual pigment
phosphorylation but not transducin translocation can contribute to
light adaptation in zebrafish cones. Neuron 41:915-28.
Tucker
C.L., Ramamurthy V., Pina A.L., Loyer M., Dharmaraj S., Li Y., Maumenee
I.H., Hurley J.B., Koenekoop R.K.. (2004). Functional analyses of
mutant recessive GUCY2D alleles identified in Leber congenital
amaurosis patients: protein domain comparisons and dominant negative
effects. Mol Vis. 10:297-303.
Nair
K.S., Hanson S.M., Kennedy M.J., Hurley J.B., Gurevich V.V., Slepak
V.Z. (2004). Direct binding of visual arrestin to microtubules
determines the differential subcellular localization of its splice
variants in rod photoreceptors. J. Biol. Chem. 279:41240-8.
Ramamurthy
V, Niemi GA, Reh TA, Hurley JB. (2004). Leber congenital amaurosis
linked to AIPL1: a mouse model reveals destabilization of cGMP
phosphodiesterase. Proc Natl Acad Sci USA 101:13897-902.
Van
Epps, H.A., Hayashi, M., Lucast, L. Stearns, G.W., Hurley, J.B., De
Camilli, P. and Brockerhoff, S.E. (2004). The zebrafish nrc mutant
reveals a role for the polyphosphoinositide phosphatase synaptojanin 1
in cone photoreceptor ribbon anchoring. J. Neurosci. 24:8641-650.
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