Michael F. Rexach
Transport of Protein and RNA across the Nuclear Pore Complex
The nuclear pore complex (NPC) is the only route for the flow of particles between the cytoplasm and the nucleoplasm; it is a supramolecular structure composed of approximately sixty proteins and is embedded in the double-membrane of the nuclear envelope. Its structure contains a central aqueous channel (25 nm in diameter) and fibers that emanate into the cytoplasm and nucleoplasm. The continuous flow of particles across the NPC is essential for cell viability as proteins that catalyze DNA replication, RNA synthesis, and ribosomal assembly must be imported into the nucleus to function. Large ribonucleoprotein complexes such as mRNA?s, ribosomal particles, and viral genomes must also move through the NPC to enter or exit the nucleus. In spite of the large diameter of the central channel movement of particles across the NPC is remarkably selective and requires energy. Traffic flows in both directions and many different transport factors function in overlapping routes of traffic.
The Rexach lab uses biochemical and genetic approaches to answer fundamental questions of the mechanics of substrate movement across the NPC. How do receptors tether such a large variety of substrates to the NPC? How are the receptors and their ligands mobilized within the aqueous cavity of the central channel? What determines the direction of transport? How is energy utilized in this process, and how are these processes regulated? An in vitro assay that reconstitutes the interaction between purified transport factors, substrates, and nucleoporins is being used to dissect the transport process into intermediate steps, and to analyze the dynamics of individual reactions.