The School of Molecular and Cellular Biology at the University of Illinois at Urbana-Champaign

The bi-directional movement of molecules between the nucleus and cytoplasm occurs through selective aqueous channels called nuclear pores. These pores are large proteinaceous complexes spanning both sides of the nuclear membrane. Nuclear transport plays an important role in cell function by selectively segregating macromolecules to the nuclear or cytoplasmic compartments. This biased distribution contributes to the regulation of many cellular processes including transcription, cell cycle, and cell signaling. In addition, regulated nuclear export of mRNA works as a quality control step to ensure that only properly spliced mRNA is exported to the cytoplasm for translation. My laboratory is interested in the mechanisms governing the translocation of proteins and RNAs through these nuclear pore complexes (NPCs). We use a wide range of biochemical, molecular and cellular approaches to dissect the mechanisms of nuclear transport. Both mammalian cells and oocytes from Xenopus laevis are used as in vivo models for our studies.

Proteins or RNAs rely on specific carrier proteins to translocate through the NPC. Following the assembly of these receptors-cargo complexes, their translocation across the NPC is mediated in part through interactions with the NPC proteins (nucleoporins). The transport receptor responsible for the export of mRNA out of the nucleus has recently been identified as Tap, a member of the NXF family of proteins. The exact mechanism behind the export of the Tap-RNA complex is not known but appears to be regulated by a second protein called Nxt1. Simple retroviruses utilize host cells machinery to replicate. Tap has been shown to mediate the export of certain viral RNAs, a necessary step for virion production. Understanding the transport mechanisms utilized during viral infections could lead to new potential therapies. Mutational analysis of Tap has revealed a number of important structural domains that modulate its interaction with the NPC or with Nxt1. The current focus of the lab is to (1) continue mutagenesis of Tap and map novel site of interaction with nucleoporins, and (2) identify novel regulators of the Tap-RNA nuclear export complex.

A novel member of the Tap/NXF family of protein, NXF5, has been associated with a form of X-linked mental retardation. NXF5 is predominantly expressed in the brain in the perinuclear and dendritic region of neurons but is absent from nuclei. This novel protein is believed to regulate mRNA transport to the dendrites. Localization of mRNA at dendrites insures efficient synthesis of proteins required for synapse formation during learning and memory acquisition. Using a neuronal cell line in culture, my laboratory is interested in deter-mining the specific function of NXF5 in mRNAs transport.