Macromolecular complexes embedded in the nuclear envelope physically
couple the cytoskeleton to the nucleus. These molecular bridges allow
the cytoskeleton to regulate nuclear position within the cell. In
addition, they provide a mechanism for signals to be mechanically
transduced between the cytoplasm and nucleus.
My laboratory is interested in investigating the role(s) of these nuclear envelope bridges in both processes. We are focused on three primary questions. First, we are defining the macromolecular components that link microtubules (and thereby microtubule-dependent force) to the nucleus.
Second, we are interested in the dynamics and mechanism by which microtubule-nuclear interfaces form and dissolve. Finally, we are investigating the means by which cytoplasmic microtubules can affect chromatin organization and dynamics, as well as the biological implications of these effects. We primarily use fission yeast as our model system, taking advantage of the outstanding imaging, biochemical and genetic tools in this organism.
Extensive Research Description
- Investigating how association of DNA double strand breaks with the LINC complex and cytoplasmic microtubules impacts genome integrity
- Testing how association of telomeres with the nuclear envelope impacts telomere maintenance
- Using advanced microscopy and force spectroscopy techniques to define the basis for the mechanical behavior of nuclei
- Probing the role that the nucleus plays in tissue level mechanics, particularly focusing on the skin.
- Schreiner SM, Koo PK, Zhao Y, Mochrie SG, King MC. The tethering of chromatin to the nuclear envelope supports nuclear mechanics. Nat Commun (2015).
- Stewart RM, Zubek AE, Rosowski KA, Schreiner SM, Horsley V, King MC. Nuclear-cytoskeletal linkages facilitate cross talk between the nucleus and intercellular adhesions. J Cell Biol (2015).
- Tran EJ, King MC, Corbett AH. Macromolecular transport between the nucleus and the cytoplasm: Advances in mechanism and emerging links to disease. Biochim Biophys Acta (2014).
- Sarah Waelde and Megan C. King. The KASH protein Kms2 coordinates mitotic remodeling of the spindle pole body. J Cell Sci. 27:3625-40 (2014).
- Rebecca K. Swartz, Elisa C. Rodriguez and Megan C. King. A role for nuclear envelope bridging complexes in homology-directed repair. MBoC. 25:2461-71 (2014).
- Megan C. King, Theodore G. Drivas, and Günter Blobel. A network of nuclear envelope membrane proteins linking centromeres to microtubules. Cell. 134, 427-38 (2008).
- Megan C. King*, C. Patrick Lusk*, and Günter Blobel. Karyopherin-mediated import of integral inner nuclear membrane proteins. Nature. 442, 1003-7 (2006).