Neuroscientists at Georgetown University Medical Center have solved a mystery that lies at the heart of human learning, and they say the solution may help explain some forms of mental retardation as well as provide clues to overall brain functioning.
Researchers have long puzzled over why a gene known as brain-derived neurotrophic factor (BDNF), which is crucial to the ability of neurons in the hippocampus to grow and connect to each other - forming the basis of memory and learning - produces two different transcripts, which then each fabricate identical proteins.
In the July 11 issue of Cell, the scientists report the answer, and it has to do with transportation. They found that the longer of the two transcripts (messenger RNAs, or mRNAs) include extra sequences that "motor" molecules attach to, in order to move the information far away from the nucleus of the cell and toward the long, tree-like branches of the nerve cell known as dendrites. There, protein-synthesizing machines use that mRNA to produce protein that helps small protrusions (called dendritic spines) on these dendrites grow.
The shorter of the mRNAs are also moved from the nucleus into the cytoplasm of the neuron, but they do not need to be transported to dendrites. These transcripts produce an identical protein, but in this case, investigators believe they help the axon, the long cable-like body of a neuron, grow.
Learning occurs when both axons and dendritic spines grow and touch each other, forming connections, and existing connections are strengthened. The scientists' findings provide a critical understanding of how dendritic spines grow and mature, but this understanding may be more broadly applied.
That's because as exciting as the findings are for understanding the function - and dysfunction - of BDNF as it relates to human learning, they also are relevant for other genes and proteins, says the study's lead investigator, Baoji Xu, Ph.D., an assistant professor in the Department of Pharmacology at Georgetown.
"The fascinating thing is that many genes produce multiple transcripts for the same protein - and no one has known why," he says. "So what we found here is likely very applicable to other genes. It reveals a mechanism for differential regulation of subcellular functions of proteins."
In this study, Xu and his research team, which included investigators from the National Institute of Child Health and Human Development (NICHHD), Emory University, and the University of Colorado, looked at why a neuron needs two "species" of BDNF mRNAs.