Transcription factors are key regulators of gene expression, and while a growing body of literature reports the presence of transcription factors in dendrites, there have been no definitive studies elucidating the functional consequences of this localization. This proposal specifically addresses the regulation and function of the transcription factor Elk-1, which is localized to both proximal and distal dendrites. By performing an in-depth characterization of a single transcription factor in dendrites, I hope to gain insight into the function of dendritic transcription factors, and further elucidate the complexities of transcriptional regulation. It is my hypothesis that transcription factors convey information about the local environment to the nucleus. More specifically, that a subset are localized near synapses, and with the appropriate activation, moved into the nucleus to influence gene transcription. This type of localization could more accurately preserve spatial, temporal and amplitude characteristics of signals coming into dendrites, in contrast to relying on more highly processed signals such as kinase cascades. By utilizing a variety of molecular techniques I will examine dendritic Elk-1 translation, trafficking, protein-protein interactions and transcriptional activity.
|Barrett, L E; Van Bockstaele, E J; Sul, J Y et al. (2006) Elk-1 associates with the mitochondrial permeability transition pore complex in neurons. Proc Natl Acad Sci U S A 103:5155-60|
|Barrett, Lindy E; Sul, Jai-Yoon; Takano, Hajime et al. (2006) Region-directed phototransfection reveals the functional significance of a dendritically synthesized transcription factor. Nat Methods 3:455-60|