Home Faculty and Research Faculty by Name Karsten Weis

Karsten Weis

Professor of Cell and Developmental Biology

Lab Homepage: http://mcb.berkeley.edu/labs/weis/

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Research Interests

Our laboratory studies the transport of macromolecules within cells. In particular, we seek to understand how proteins and RNAs are transported across the nuclear envelope. The exchange of macromolecules between the nucleus and the cytoplasm is absolutely essential to establish and maintain order in eukaryotic cells, and constitutes an important step in the regulation of gene expression. Our laboratory combines genetic, biochemical and biophysical approaches in Saccharomyces cerevisiae and in metazoan cells to characterize and analyze the molecular machinery that is responsible for the transport of macromolecules into and out of the nucleus.

Interestingly, components of the nuclear transport machinery function not only to transport cargo during interphase but also play essential roles in cell division. In particular, the small GTPase Ran has emerged as a key regulator signaling multiple chromatin-mediated events during mitosis. We would like to understand the function of Ran in mitosis as well as identify and characterize factors that are regulated by Ran during cell division.

Current Projects

Nuclear transport. Compartmentalization in eukaryotes causes spatial separation of cellular processes such as DNA transcription and mRNA translation. This leads to the bi-directional exchange of a large number of macromolecules between the nuclear and cytoplasmic compartments and allows for additional regulation of eukaryotic gene expression. The nuclear pore complex (NPC), a gigantic multi-protein structure, mediates nucleocytoplasmic transport. Our laboratory is working to understand the molecular principles governing transport events across the NPC. Using various approaches, we aim to dissect the roles of NPC components and soluble transport factors, with the ultimate goal of understanding how protein and RNA complexes are directionally transported across the nuclear envelope.

Mitotic role of the RanGTPase. In a collaboration with the laboratory of Rebecca Heald, we study how the small GTPase Ran regulates cell division. Ran is a highly conserved and abundant protein, which, like other members of the family of small GTPases, continually cycles between GTP- and GDP-bound forms. Using a FRET-based RanGTP biosensor we have shown that RanGTP is enriched around chromatin where it locally liberates cargoes from transport receptors, promoting spindle assembly during mitosis. We have identified mitotic cargoes that are regulated by the RanGTP pathway, leading to the unexpected discovery that RNA is required for spindle organization and function. Currently, we are dissecting the novel functions of RNA in spindle assembly and continuing to characterize effectors of the Ran pathway during mitosis.

Selected Publications

Weirich, C.S., Erzberger, J.P., Flick, JS, Berger, J.M., Thorner, J., Weis, K. (2006) Local Activation of the DExD/H-box protein Dbp5 by the nuclear pore protein Gle1 and its coactivator inositol hexakisphosphate is required for mRNA export. Nature Cell Biol, 8: 668-676.

Kalab P, Pralle A, Isacoff EY, Heald R, Weis K. (2006) Analysis of a RanGTP-regulated gradient essential for mitosis in somatic cells. Nature, 440: 607-701.

Madrid AS, Mancuso J, Cande WZ, Weis K. (2006) The role of the integral membrane nucleoporins Ndc1p and Pom152p in nuclear pore complex assembly and function. J Cell Biol, 173: 361-371.

Madrid AS, Weis K. (2006) Nuclear transport is becoming crystal clear. Chromosoma, 115: 98-109.

Blower, M.D., Nachury, M.V., Heald, R. and Weis, K. (2005) A Rae1-containing ribonucleoprotein complex is required for mitotic spindle assembly. Cell, 121: 223-234.

Brune, C., Munchel, S. E., Fischer, N., Potdtelejnikov, A.V., Weis K. (2005) Yeast poly (A)-binding protein Pab1 shuttles between the cytoplasm and the nucleus and functions in mRNA export. RNA, 4: 517-531.

Weirich, C.S., Erzberger, J.P., Berger, J.M., Weis, K. (2004) The N-terminal domain of Nup159 forms a β-propeller that functions in mRNA export by tethering the helicase Dbp5 to the nuclear pore. Molecular Cell, 16: 749-760.

Zeitler, B., Weis, K. (2004) The asymmetry of FG-repeat nucleoporins is dispensable for bulk transport through the nuclear pore complex in vivo. J Cell Biol, 167: 583-590.

Weis, K. (2003) Regulating access to the genome: nucleocytoplasmic transport throughout the cell cycle. Cell, 112: 441-451.

Kalab, P., Weis, K., Heald, R. (2002) Visualization of a RanGTP gradient in interphase and mitotic Xenopus egg extracts. Science, 295: 2452-2456.

Nachury, M.V., Maresca, T.J., Salmon, W.C., Waterman-Storer, C.M., Heald, R. and Weis, K. (2001) Importin β is a mitotic target of the small GTPase Ran in spindle assembly. Cell, 104: 95–106.

Last Updated 2006-08-22