Within each human cell is a nucleus, “mothership” of the human genome and still the least-understood cellular structure. Chromosomes are enclosed by the nuclear envelope (NE) and communicate with the cytoplasm through Nuclear Pore Complexes (NPCs). The inner and outer membranes of the NE are mechanically connected by SUN-domain proteins and nesprins, which form LINC (links the nucleoskeleton and cytoskeleton) complexes. LINC complexes are anchored to nuclear intermediate filament (nuclear ‘lamina’) networks. Together the NE and nuclear lamina protect, organize and help regulate chromatin.
Research in the Wilson lab centers on the three key components of nuclear lamina structure: lamins, LEM-domain proteins, and BAF (Barrier to autointegration factor, encoded by BANF1). Mutations in one or more of these proteins cause a variety of diseases including Emery-Dreifuss muscular dystrophy (EDMD), cardiomyopathy, lipodystrophy/diabetes and ‘accelerated aging’ (progeria syndromes).
Loss of emerin typically causes X-linked recessive EDMD. Emerin protein is expressed throughout the body, but EDMD affects only three tissues, with contractures of major tendons, slowly progressive muscle wasting, and ventricular conduction defects that can cause sudden cardiac arrest. EDMD can also be caused by mutations in at least five other proteins including A-type lamins, nesprin-1, nesprin-2, LUMA (a membrane protein that associates with emerin), and FHL1 (a muscle-relevant transcription factor). Since most of these proteins interact, defects in a mechano-transduction signaling complex that includes these proteins might contribute to disease.
Current work aims to understand emerin’s role in mechanotransduction, how emerin and lamin A are regulated, and whether misregulation contributes to disease.
Bar DZ, Davidovich M, Lamm AT, Zer H, Wilson KL and Gruenbaum Y. “BAF-1 mobility is regulated by environmental stresses.” Molecular Biology of the Cell 25:1127-36. 2014.
Berk JM, Simon DN, Jenkins-Houk CR, Westerbeck JW, Gronning-Wang LM, Carlson CR and Wilson KL. "The molecular basis of emerin-emerin and emerin-BAF interactions." J. Cell Science 127:3956-69. 2014.
Berk JM, Tifft KE and Wilson KL. “The nuclear envelope LEM-domain protein emerin.” Nucleus 4:1-17. 2013.
Berk JM, Maitra S, Dawdy AW, Shabanowitz J, Hunt DJ and Wilson KL. “O-GlcNAc regulates emerin binding to BAF in a chromatin- and lamin B-enriched ‘niche’.” J. Biological Chemistry 288:30192-209. 2013.
Simon DN and Wilson KL. “Partners and posttranslational modifications of nuclear lamins.” Chromosoma 122:13-31. 2013.
Wozniak M, Baker BM, Chen C and Wilson KL. “Emerin-binding transcription factor Lmo7 is regulated by association with p130Cas at focal adhesions.” PeerJ e134, 2013.
Simon DN, Domaradzki T, Hofmann WA and Wilson KL. "Lamin A tail modification by SUMO1 is disrupted by familial partial lipodystrophy-causing mutations." Molecular Biology of the Cell 24:342-50. 2013.
Gjerstorff MF, Rosner HI, Pedersen CB, Greve KB, Schmidt S, Wilson KL, Mollenhauer J, Besir H, Poulsen FM, Mollegaard NE and Ditzel HJ. "GAGE cancer-germline antigens are recruited to the nuclear envelope by germ cell-less (GCL)." PLoS One 7:e45819. 2012.
Barkan R, Zahand AJ, Sharabi K, Lamm AT, Feinstein N, Haithcock E, Wilson KL, Liu J and Gruenbaum Y. "Ce-emerin and LEM-2: essential roles in Caenorhabditis elegans development, muscle function, and mitosis." Molecular Biology of the Cell 23:543-52. 2012.
Montes de Oca R, Andreassen PR and Wilson KL. "Barrier-to-Autointegration Factor influences specific histone modifications." Nucleus 2:580-90. 2011.
Simon DN and Wilson KL. "The nucleoskeleton as a genome-associated dynamic 'network of networks'." Nature Reviews Molecular Cell Biology 12:695-708. 2011.
Wilson KL and Dawson SC. "Evolution: Functional evolution of nuclear structure." J. Cell Biology 195:171-81. 2011.