Scientists Identify A Mechanism That Helps Fruit Flies Lock-In Memories
A protein called Pum regulates the expression of genes that alter synaptic
plasticity
To lock in a memory, nerve cells must strengthen their connections with some
neighbors but not others. Three research groups at Cold Spring Harbor Laboratory
(CSHL) have collaborated to identify a protein whose action helps alter the
strength of synaptic connections in fruit flies as they form memories.
Synapses are the tiny gaps across which information crosses between nerve
cells. Changes in the strength of synaptic connections, called plasticity, play
a vital role in both memory formation and learning, and help determine how nerve
signals propagate.
Assistant professor Josh Dubnau, Ph.D., leads a CSHL neuroscience lab that
studies learning and memory in fruit flies, or Drosophila. His team had
previously identified a group of fly genes needed for memory formation,
including one called Pumilio. A similar gene is present in humans, so studying
Pumilio in the fly brain could help researchers understand how memory works in
the human brain.
A Fruitful Hypothesis
Prior work had shown that Pumilio acts with other genes to shape the
developing fly embryo, by modifying how much of various proteins is made in
different regions of a cell. Dr. Dubnau hypothesized that the gene acts
similarly to affect memory formation.
To further explore this idea, Dr. Dubnau collaborated with CSHL Professors
Michael Zhang, Ph.D., a computational biologist, and Adrian Krainer, Ph.D., an
expert on gene expression. He posed a question to Dr. Zhang that called for
sophisticated mathematical analysis: For 151 genes known to be active in
synapses, which of the protein-precursors they produce were most likely to
interact with Pum, the protein made by Pumilio? Back in the laboratory, Dr.
Krainer’s team confirmed that Pum interacts with several of the
protein-precursors identified by Dr. Zhang’s team, including one arising from
a gene called dlg1. A gene very similar to dlg1 acts in synapse formation in
mammals.
Testing the Result in Living Flies
What about the fly? Dr. Dubnau’s lab performed the final step. They
genetically engineered flies that made especially large amounts of Pum protein
in a brain region called the mushroom body where memory storage occurs. They
then confirmed that, in such flies, the protein product of the dlg1 gene was
dramatically reduced in this brain region. This observation supports the notion
that Pumilio helps build memories by selectively altering individual synapses.
The current work is particularly satisfying, Dr. Dubnau noted, because the
original hypothesis about Pumilio was extended by computations to make further
predictions, which were then brought full circle and tested in vitro, in the lab
and in vivo, in living flies. "It's the kind of interdisciplinary
collaboration that Cold Spring Harbor is very good at," he observed.
More information:
 For
more information, visit www.cshl.edu.
Contact:
Jim Bono
516-367-8455
bono@cshl.edu
“Identification of Synaptic Targets of Drosophila Pumilio” appears in
PLoS Computational Biology on February 29, 2008. The paper is available online
at:
http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1000026
Cold Spring Harbor Laboratory is a private, non-profit research and education
institution dedicated to exploring molecular biology and genetics in order to
advance the understanding and ability to diagnose and treat cancers,
neurological diseases and other causes of human suffering.
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