"In addition to showing that mRNA splicing occurs in dendrites in which we added mRNA, we also detected the resulting protein," notes Eberwine. "Since the splicing machinery is present in dendrites, one could speculate that if pre-mRNA is present naturally in the dendrite, when activated, it may be spliced and translated, giving rise to many different proteins."

Protein diversity is a key aspect to the complexity of the central nervous system. Proteins are the workhorses of the cell and are generally responsible for insuring that cells function properly. When proteins interact with one another they can elicit specific physiological responses, including the generation and maintenance of memories. Changing protein identity, as can occur with splicing, can change the ability of the protein to interact with other proteins and therefore potentially change such physiological processes. With the dendrite being the initial site in the neuron where learning is thought to occur, the ability to create a diversity of mRNAs, through local splicing, and subsequent protein translation may permit exquisitely sensitive control of these cellular functions.

"The regulation and timing of the expression of proteins is what makes the central nervous system function," says Eberwine. The diversity and redundancy of the nervous-system proteins may serve to help maintain the system over a lifetime. However, failure in protein regulation or proper expression in neurons may give rise to cognitive dysfunction. "Most neurodegenerative and psychiatric illnesses exhibit dendrite dysfunction, therefore, the inability to properly generate spliced RNAs in dendrites or proteins may underlie aspects of these disease processes
'"/>

Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
7-Nov-2005