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Process leading to protein diversity in cells important for proper neuron firing
Date:11/18/2010

tained introns are necessary to produce a functional ion channel called BKCa in the dendrite. BKCa channels need to have these introns spliced out in the cytoplasm to work correctly. Introns were once thought of as junk DNA, but are now being shown to exert important regulatory control. Indeed, in some cases mutations in introns are responsible for causing disease, while in previous work Eberwine and colleagues were able to show that a retained intron is responsible for proper cellular localization of the final translated protein.

One particular intron, i17a, is found next to a portion of the BKCa protein, called the STREX domain. When STREX is in the channel protein BKCa, physiological properties such as burst firing and action potential change. These are important bio-electrical actions governing how nerve cells communicate with each other.

For the STREX domain to be part of the larger BKCa protein, i17a has to be removed in the cytoplasm. If i17a isn't spliced out in the cytoplasm very little STREX-containing BKCa protein is made. This leads to a poorly functioning neuron.

Diseases such as epilepsy that are based on electrical misfiring in the brain could be targets of manipulating cytoplasmic splicing to control how much STREX-containing BKCa protein is made and ultimately available in a neuron cell membrane. The diversity in splicing allows for different types of protein to be made, including the STREX-containing protein. In turn, other proteins are then able to bind to the channel, which in turn leads to other molecular events necessary for correct nerve firing.

The generality of this phenomena is being investigated with the goal being to understand this form of cellular regulation such that it can be experimentally manipulated in a directed and meaningful manner.


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Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
Source:Eurekalert  

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