The researchers then overexpressed Elk-1 in rat neurons to see if there was an effect on cell viability. "We thought that through interaction with Elk-1, the mitochondria would be able to regulate cell death," says Eberwine. "By overexpressing Elk-1, we found that we did decrease cell viability, achieving more cell death. Conversely, when we knock-down Elk-1 expression, the survivability of neurons increased, which indicates that Elk-1 plays a role in neuron viability."

Cell-death is a component of a number of psychiatric and neurological diseases such as schizophrenia and those that involve neurodegeneration. For many of these diseases dysfunction of the dendrite is also associated with the disease process. "Therefore, anything that impacts dendrite function might be associated with illness," surmises Eberwine. "The fact that Elk-1 RNA and protein are present in dendrites, and the fact that Elk-1 can modulate cell viability, potentially through the mitochondria, suggests that Elk-1 could play a role in these diseases perhaps through modulation of mitochondrial activity."

To more precisely understand the role of Elk-1 RNA in the dendrite, the researchers developed a method called phototransfection, which was described in their June Nature Methods paper, to focally introduce Elk-1 RNA into the dendrite. In this technique, a laser light beam is used to create small transient pores in the membrane of intact rat nerve cells, into which a known amount of RNA molecules are introduced by diffusion.

The introduction and translation of Elk-1 mRNA in dendrites by phototransfection also elicited cell death whereas introduction and translation of Elk-1 mRNA
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Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
7-Jun-2006