Ph.D. University of Texas Southwestern Medical Center at Dallas
In the central nervous system, each neuron receives thousands of synaptic connections from others and modifies the strength of individual synapses independently with varying degrees of stability. This experience-dependent synaptic plasticity underlies the molecular and cellular basis of learning and memory. Accumulating evidence has suggested that regulated translation of localized mRNAs at specific synapses is one of mechanisms that modify long-term plasticity and memory. Several RNA-binding proteins have been implicated in targeting specific mRNAs to dendrites and/ or regulating translation in response to synaptic activity. Among them is CPEB (cytoplasmic polyadenylation element binding protein), which promotes dendritic transport and polyadenylation-induced translation of CPE-containing (UUUUAU or similar) mRNAs. The study of how CPEB functions in neurons suggests a plausible model whereby transport and translation of specific mRNAs can be regulated by their cognate RNA-binding proteins with spatial and temporal precision to influence plasticity at the stimulated synapse, thereby stably modifying only that connection. Thus, the study of RNA-binding proteins in synaptic translational control will help identifying proteins (i.e. molecular molecules of memory) involved in plasticity, learning and memory. The current focus in the lab is to characterize other CPEB family members, CPEBs2-4, in the mammalian neurons.