We propose to continue studying the intermediate filament (IF) based cytoskeletal system in mammalian cells. Emphasis will be placed on the regulation of the organization of IF and their interactions with the nuclear surface. The long term goal of these studies is to determine the possible functions of the IF system and its interaction with the nucleus, now known to contain another IF protein family system known as the nuclear lamins. The experimental plan involves detailed morphological studies on the coordinated activities of the cytoplasmic IF and nuclear surface systems throughout the cell cycle using immunocytochemical techniques, biochemical and physiological analyses, the effects of phosphorylation on the cytoplasmic IF system, structural studies of the nuclear lamin paracrystals, and the use of microinjection of derivatized IF proteins. The IF system is thought to be involved in various physiological activities, including nuclear-cytoplasmic interactions, signal processing between the cell surface and the nucleus, etc. With regard to disease processes, this system is frequently found in an altered state in many diseases including cancer, Alzheimers disease, liver diseases and several other neurological disorders.
| Takeshi, Shimi; Pack, Chan-Gi; Goldman, Robert D (2016) Analyses of the Dynamic Properties of Nuclear Lamins by Fluorescence Recovery After Photobleaching (FRAP) and Fluorescence Correlation Spectroscopy (FCS). Methods Mol Biol 1411:99-111 |
| Butin-Israeli, Veronika; Adam, Stephen A; Jain, Nikhil et al. (2015) Role of lamin b1 in chromatin instability. Mol Cell Biol 35:884-98 |
| Shimi, Takeshi; Goldman, Robert D (2014) Nuclear lamins and oxidative stress in cell proliferation and longevity. Adv Exp Med Biol 773:415-30 |
| Guo, Yuxuan; Kim, Youngjo; Shimi, Takeshi et al. (2014) Concentration-dependent lamin assembly and its roles in the localization of other nuclear proteins. Mol Biol Cell 25:1287-97 |
| Funkhouser, Chloe M; Sknepnek, Rastko; Shimi, Takeshi et al. (2013) Mechanical model of blebbing in nuclear lamin meshworks. Proc Natl Acad Sci U S A 110:3248-53 |
| Adam, Stephen A; Butin-Israeli, Veronika; Cleland, Megan M et al. (2013) Disruption of lamin B1 and lamin B2 processing and localization by farnesyltransferase inhibitors. Nucleus 4:142-50 |
| Butin-Israeli, Veronika; Adam, Stephen A; Goldman, Robert D (2013) Regulation of nucleotide excision repair by nuclear lamin b1. PLoS One 8:e69169 |
| Shimi, Takeshi; Butin-Israeli, Veronika; Goldman, Robert D (2012) The functions of the nuclear envelope in mediating the molecular crosstalk between the nucleus and the cytoplasm. Curr Opin Cell Biol 24:71-8 |
| Butin-Israeli, Veronika; Adam, Stephen A; Goldman, Anne E et al. (2012) Nuclear lamin functions and disease. Trends Genet 28:464-71 |
| Adam, Stephen A; Goldman, Robert D (2012) Insights into the differences between the A- and B-type nuclear lamins. Adv Biol Regul 52:108-13 |
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