Johns Hopkins researchers have discovered a gene in
fruit flies that helps certain specialized neurons respond
more quickly to bright light. The study, published in the
April 4 issue of Current Biology, also has
implications for understanding sensory perception in
mammals.
In teasing apart the molecular interactions and
physiology underlying light perception, the researchers
studied a gene they dubbed "Lazaro" that is expressed 15
times higher in the fly eye than the rest of the fly head.
They found that this gene is required for a second
biochemical pathway that controls the activity of a protein
called the TRP channel. TRP channels are found in fruit fly
neurons responsible for sensing light. The fly TRP channel
is the founding member of a family of related proteins in
mammals that are essential for guiding certain nerves
during development and for responding to stimuli including
heat, taste and sound.
By shining bright light onto and recording electrical
changes in single nerve cells in the fly eye, researchers
found that neurons carrying a mutation in this gene cannot
respond as well to light as can neurons carrying normal
copies of this gene. In fact, the mutant neurons turn off
their response to light four times faster than normal
neurons do. Because Lazaro helps fly TRP channels work at
their maximum, it is possible that a Lazaro-like gene in
mammals might also play a role in how well mammalian TRP
channels work.
"These results have implications for understanding
sensory signaling in mammals," said the study's senior
author,
Craig Montell, a professor in the
Biological
Chemistry Department in the Institute of Basic
Biomedical Sciences at Johns Hopkins.
The researchers also discovered that alterations in
this new gene greatly reduce the retinal degeneration
caused by a different mutant. They named this new gene
Lazaro after the novel Lazarillo de Tormes, in which the
orphan boy Lazaro helps a blind man see.
Of the molecules known to control TRP channels, a key
player is diacylglycerol, or DAG. DAG is known to be made
by a well-studied biochemical pathway. The researchers
found that Lazaro provides a second way to make DAG,
enabling the cell to make more DAG.
Why is there a second pathway for DAG production? "We
think Lazaro is priming the system for maximal light
response," Montell said.
DAG can be metabolized to polyunsaturated fatty acids,
which have been shown to control TRP channels in flies and
may also control some mammalian TRP channels. However,
exactly how these molecules exert their control remains
unclear. In adding the Lazaro gene to the list of players,
the researchers hope to learn more about how TRP channels
are controlled.
The researchers were funded by the National Eye
Institute.
Authors on the paper are Young Kwon and Montell, both
of Johns Hopkins.