Office: 454A Morrill IV South
B.S., University of Iowa, 1994
Ph.D., Johns Hopkins University, 2000
Washington University at St. Louis, 2000-2005
Mechanism of Dynein-Mediated Nuclear Migration and Spindle Positioning
During all eukaryotic cell divisions, the mitotic spindle must be positioned properly to ensure faithful segregation of cellular determinants into the progeny cells. My lab aims at understanding how dividing cells know where to position the mitotic spindle, and what mechanism they use to move the mitotic spindle to the proper location.
We use the budding yeast Saccharomyces cerevisiae as our experimental system. Yeast supports a unique combination of classical and molecular genetic studies, high resolution in vivo imaging, and biochemical approaches. Current studies aim at understanding how cytoplasmic microtubules, the microtubule motor dynein and its regulator dynactin, and the cortical attachment protein Num1 in mediating movement of the mitotic spindle into the mother-bud neck. This network of cytoskeletal and regulatory proteins, termed the dynein pathway components, function in the bud to pull the mitotic spindle into the neck. Positioning of the spindle across the neck guarantees that the daughter and mother cells receive an exact copy of the duplicated chromosomes prior to cytokinesis. Our results show that, during the dynein pathway, dynamic astral/cytoplasmic microtubules probe the bud cortex for attachment sites containing the cortical protein Num1 and other associated proteins. Dynein is targeted to the distal plus ends of these cytoplasmic microtubules, and its localization is dependent on the its regulator Pac1, the yeast homologue of human LIS1. Our results suggest that upon productive interactions between the distal ends of microtubules and cortical attachment sites, dynein is offloaded, anchored and subsequently activated to be utilized in force production for pulling the mitotic spindle into the neck.
Bezanilla M., Gladfelter A.S., Kovar D.R., W.-L. Lee. 2015. Cytoskeletal dynamics: a view from the membrane. J Cell Biol, 209(3):329-37.
Markus S.M., Omer S., Baranowski K., W.-L. Lee. 2015. Improved Plasmids for Fluorescent Protein Tagging of Microtubules in Saccharomyces cerevisiae. Traffic, Jul;16(7):773-86.
Zhu Y, W.-L. Lee. 2014. The role of +TIPs in directional tip expansion. Mol Microbiol, Nov;94(3):486-9.
Wadsworth P. and W.-L. Lee. 2013. Microtubule motors: doin’ it without dynactin. Curr Biol, Jul 8, 23(13):R563-565.
Markus, S.M., K.A. Kalutkiewicz, and W.-L. Lee. 2012. She1-mediated Inhibition of Dynein Motility along Astral Microtubules Promotes Polarized Spindle Movements. Curr Biol, Dec 4, 22(23):2221-2230.
Collins E.S., Balchand S.K., Faraci J.L., Wadsworth P., and W.-L. Lee. 2012. Cell Cycle-Regulated Cortical Dynein/Dynactin Promotes Symmetric Cell Division by Differential Pole Motion in Anaphase. Mol Biol Cell, 23(17):3380-3390.
Markus S.M., Kalutkiewicz K.A., and W.-L. Lee. 2012. Astral microtubule asymmetry provides directional cues for spindle positioning in budding yeast. Exp Cell Res, 318(12):1400-1406.
Tang X.Y., St. Germain B.J., and W.-L. Lee. 2012. A Novel Patch Assembly Domain in Num1 Mediates Dynein Anchoring at the Cortex during Spindle Positioning. J Cell Biol, 196:743–756.
Markus, S.M. and W.-L. Lee. 2011. Regulated Offloading of Cytoplasmic Dynein from Microtubule Plus Ends to the Cortex. Developmental Cell, 20(5): 639-651.
Markus, S.M., Plevock, K.M, Germain, B.S., Punch, J.J, Meaden, C.W., and W.-L. Lee. 2011. Quantitative Analysis of Pac1/LIS1-Mediated Dynein Targeting: Implications for Regulation of Dynein Activity in Budding Yeast. Cytoskeleton, 68(3): 157-174.
Lee W.-L. and P. Wadsworth. 2009. New Spindle Morphogenesis Model by Dynein, Nudel, and the Spindle Matrix. Research Highlight. Cell Research, 19(5): 529-531.
Markus, S.M., J.J. Punch, and W.-L. Lee. 2009. Motor- and Tail-Dependent Targeting of Dynein to Microtubule Plus Ends and the Cell Cortex. Curr Biol, 19(3): 196-205.
Tang, X.Y., J.J. Punch, and W.-L. Lee. 2009. A CAAX Motif can Compensate for the PH domain of Num1 for Cortical Dynein Attachment. Cell Cycle, 8(19): 3182-3190.
Vorvis, C., S.M. Markus, and W.-L. Lee. 2008. Photoactivatable GFP tagging cassettes for protein-tracking studies in the budding yeast Saccharomyces cerevisiae. Yeast, 25: 651-659.
Lee W.L., M.A. Kaiser, and J.A. Cooper. 2005. The offloading model for dynein function: differential function of motor subunits. J Cell Biol, 168: 201-207.
Li, J., W.L. Lee, and J.A. Cooper. 2005. NudEL targets dynein to microtubule ends through LIS1. Nat Cell Biol, 7: 686-690.
Lee W.L., J.R. Oberle, and J.A. Cooper. 2003. The role of the lissencephaly protein Pac1 during nuclear migration in budding yeast. J Cell Biol, 160: 355-364.
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